Page last updated: 2024-12-05

pilocarpine

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Description

Pilocarpine: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

(+)-pilocarpine : The (+)-enantiomer of pilocarpine. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID5910
CHEMBL ID550
CHEBI ID8207
CHEBI ID39462
SCHEMBL ID15146
MeSH IDM0016860

Synonyms (134)

Synonym
BIDD:GT0217
AB00053525-27
BRD-K85090592-008-05-2
gtpl305
KBIO1_000358
DIVK1C_000358
NCI60_004403
SDCCGMLS-0003164.P005
pilokarpol
ocusert pilo-20
2(3h)-furanone, 3-ethyldihydro-4-((1-methyl-1h-imidazol-5-yl)methyl)-, (3s-cis)-
ai3-50523
ocusert p 20
pilocarpin
(3s-cis)-3-ethyldihydro-4-((1-methyl-1h-imidazol-5-yl)methyl)-2(3h)-furanone
imidazole-5-butyric acid, alpha-ethyl-beta-(hydroxymethyl)-1-methyl-, gamma-lactone
pilocarpol
ocusert pilo-40
hsdb 3163
einecs 202-128-4
pilokarpin
2(3h)-furanone, 3-ethyldihydro-4-((1-methyl-1h-imidazol-5-yl)methyl)-, (3s,4r)-
syncarpine
ocusert pilo
SPECTRUM_001107
NCGC00023339-03
tocris-0694
PRESTWICK2_000449
(3s,4r)-3-ethyl-4-[(3-methylimidazol-4-yl)methyl]tetrahydrofuran-2-one
pilocarpine nitrate salt
SPECTRUM5_001379
BPBIO1_000548
LOPAC0_000960
PRESTWICK3_000449
BSPBIO_002191
IDI1_000358
pilocarpine
92-13-7
C07474
CHEBI:8207 ,
(3s,4r)-3-ethyldihydro-4-((1-methyl-1h-imidazol-5-yl)methyl)-2(3h)-furanone
(3s-cis)-3-ethyldihydro-4-[(1-methyl-1h-imidazol-5-yl)methyl]-2(3h)-furanone
(+)-pilocarpine
(3s,4r)-3-ethyl-4-[(1-methyl-1h-imidazol-5-yl)methyl]dihydrofuran-2(3h)-one
DB01085
D00525
ocusert pilo-20 (tn)
pilocarpine (jan/usp)
BSPBIO_000498
NCGC00023339-09
KBIOSS_001587
KBIO3_001691
KBIO2_006723
KBIO2_004155
KBIOGR_000956
KBIO2_001587
PRESTWICK0_000449
SPBIO_001287
SPBIO_002437
PRESTWICK1_000449
NINDS_000358
SPECTRUM2_001284
SPECTRUM4_000478
SPECTRUM3_000546
LOPAC0_000950
NCGC00023339-06
NCGC00023339-08
NCGC00023339-07
HMS2089K17
NCGC00023339-12
NCGC00023339-13
pilocarpinum
ocucarpine
spersacarpine
CHEMBL550 ,
bdbm50008072
(3s,4r)-3-ethyl-4-[(3-methylimidazol-4-yl)methyl]oxolan-2-one
NCGC00023339-10
NCGC00023339-14
NCGC00023339-11
dtxcid901162
tox21_110887
cas-92-13-7
dtxsid1021162 ,
CCG-205031
AKOS016010311
beta-pilocarpine hydrochloride
pilocarpine [usp:ban:jan]
01mi4q9di3 ,
unii-01mi4q9di3
pilocarpine [mi]
pilocarpine [usp-rs]
pilocarpine [usp monograph]
pilocarpine [hsdb]
pilocarpine [vandf]
pilocarpine [orange book]
pilocarpine [mart.]
pilocarpinum [hpus]
pilocarpine [who-dd]
pilocarpine [jan]
SCHEMBL15146
NCGC00023339-16
tox21_110887_1
2(3h)-furanone, 3-ethyldihydro-4-[(1-methyl-1h-imidazol-5-yl)methyl]-, (3s,4r)-
(3s,4r)-3-ethyl-4-((1-methyl-1h-imidazol-5-yl)methyl)dihydrofuran-2(3h)-one
AB00053525_29
AB00053525_28
mfcd00153042
(3s,4r)-3-ethyl-4-[(1-methyl-1h-imidazol-5-yl)methyl]oxolan-2-one
SR-01000075339-11
SBI-0050924.P004
Q411461
92-13-7 (free base)
102282-25-7
BRD-K85090592-008-15-1
SDCCGSBI-0050924.P006
NCGC00023339-28
NCGC00023339-27
pilocarpine 100 microg/ml in acetonitrile
BS-18966
pilocarpine, cytokine
HY-B0726A
CS-0013746
E87145
EN300-19632236
pilocarpine (usp-rs)
(3s-cis)-3-ethyldihydro-4-
rel-(3r,4s)-3-ethyl-4-((1-methyl-1h-imidazol-5-yl)methyl)dihydrofuran-2(3h)-one
pilocarpine (mart.)
pilocarpine (usp monograph)
(3s,4r)-3-ethyl-4-(1-methyl-1h-imidazol-5-ylmethyl)-4,5-dihydrofuran-2(3h)-one
pilocarpine (usp:ban:jan)
pilocarpina
chebi:39462

Research Excerpts

Overview

Pilocarpine is an accepted treatment for xerostomia, but limited research has been conducted on the oral, topical form. It is a nonselective muscarinic agonist that is used clinically, but has not been well characterized for its actions during cocaine-reinforced behavior.

ExcerptReferenceRelevance
"Pilocarpine is an accepted treatment for xerostomia, but limited research has been conducted on the oral, topical form. "( Comparison of the 1 and 2% pilocarpine mouthwash in a xerostomic population: a randomized clinical trial.
Alaee, A; Azizi, A; Fard, MJK; Jafari, A; Jahandar, H; Motamed, B, 2022
)
2.46
"Pilocarpine is an M3 muscarinic agonist that is widely used for the treatment of xerostomia caused by various diseases and medical conditions. "( Pilocarpine induces the residual secretion of salivary fluid in perfused submandibular glands of rats.
Murakami, M; Narita, T; Qi, B; Sugiya, H, 2019
)
3.4
"Pilocarpine is a nonselective muscarinic agonist that is used clinically, but has not been well characterized for its actions during cocaine-reinforced behavior."( The muscarinic agonist pilocarpine modifies cocaine-reinforced and food-reinforced responding in rats: comparison with the cholinesterase inhibitor tacrine.
Grasing, KW; Idowu, JY; Xu, H, 2019
)
1.55
"Pilocarpine is an alkaloid obtained from the leaves of Pilocarpus genus, with important pharmaceutical applications. "( Characterisation of the membrane transport of pilocarpine in cell suspension cultures of Pilocarpus microphyllus.
Abreu, IN; Andreazza, NL; Mazzafera, P; Sawaya, AC, 2015
)
2.12
"Pilocarpine is a substrate of PGP and BCRP at the rodent blood-brain barrier, which restricts its convulsive action."( Pilocarpine-induced convulsive activity is limited by multidrug transporters at the rodent blood-brain barrier.
Bankstahl, JP; Bankstahl, M; Löscher, W; Römermann, K, 2015
)
2.58
"Pilocarpine is a cholinergic agent that promotes salivation."( Testing pilocarpine drops for dry mouth in advanced cancer using n-of-1 trials: A feasibility study.
Agar, M; Carmont, SA; Currow, D; Good, P; Hardy, J; Mitchell, GK; Nikles, J; Schluter, PJ; Senior, H; Vora, R, 2015
)
1.57
"Pilocarpine is a cholinergic agonist that increases salivary flow rate and has been used to treat xerostomia."( Effects of benzodiazepine and pilocarpine on rat parotid glands: histomorphometric and sialometric study.
Azevedo-Alanis, LR; Bertassoni, LE; D'Agulham, AC; de Lima, AA; Grégio, AM; Machado, MA; Zaclikevis, MV, 2009
)
1.36
"Pilocarpine is an imidazole alkaloid that has been used for more than a century in glaucoma treatment. "( Metabolic alterations in different developmental stages of Pilocarpus microphyllus.
Abreu, IN; Choi, YH; Eberlin, MN; Mazzafera, P; Sawaya, AC; Verpoorte, R, 2011
)
1.81
"Pilocarpine is a nonspecific agonist of muscarinic receptors which was recently found to activate the M(2) receptor subtype in a voltage-dependent manner. "( Muscarinic-activated potassium current mediates the negative chronotropic effect of pilocarpine on the rabbit sinoatrial node.
Aréchiga-Figueroa, IA; Moreno-Galindo, EG; Navarro-Polanco, RA; Rodríguez-Martínez, M; Sánchez-Chapula, JA, 2011
)
2.04
"Pilocarpine-treated mice are an increasingly used model of temporal lobe epilepsy. "( Factors affecting outcomes of pilocarpine treatment in a mouse model of temporal lobe epilepsy.
Buckmaster, PS; Haney, MM, 2012
)
2.11
"Pilocarpine, which is an M2R stimulant, increased the density of M3R in the lung tissue and the rate of the increase in sensitized guinea pigs was less than that in the control group."( Role of muscarinic acetylcholine receptors in a guinea pig model of asthma.
Fukuoka, M; Haraguchi, R; Itoh, M; Kubo, H; Nakajima, S; Ohkawa, K; Tohda, Y, 2002
)
1.04
"Pilocarpine is a useful agent as a treatment of radiation-induced xerostomia in head and neck cancer patients."( Evaluation, prevention and management of radiotherapy-induced xerostomia in head and neck cancer patients.
de Castro, G; Federico, MH, 2006
)
1.06
"Pilocarpine is a cholinergic agonist commonly used to induce seizures and an epilepticus-like state in rodents."( Antioxidant response analysis in the brain after pilocarpine treatments.
Esteban, S; Gamundí, A; Rial, RV; Roca, C; Sureda, A; Tejada, S, 2006
)
1.31
"Pilocarpine is a cholinergic agonist that is metabolized to pilocarpic acid by serum esterase. "( Involvement of CYP2A6 in the formation of a novel metabolite, 3-hydroxypilocarpine, from pilocarpine in human liver microsomes.
Ban, M; Endo, T; Hara, Y; Hirata, K; Momose, Y; Yamamoto, A, 2007
)
2.02
"Pilocarpine is a cholinergic agonist capable to induce seizures and an epilepticus-like state in rodents. "( Antioxidant response and oxidative damage in brain cortex after high dose of pilocarpine.
Esteban, S; Gamundí, A; Roca, C; Sureda, A; Tejada, S, 2007
)
2.01
"Pilocarpine is a cholinergic agonist which stimulates salivary secretion both in individuals with normal salivary gland function and in those with impaired salivary flow (xerostomia or oral dryness). "( Oral pilocarpine: a review of its pharmacological properties and clinical potential in xerostomia.
Faulds, D; Wiseman, LR, 1995
)
2.25
"1. Pilocarpine is a cholinomimetic natural alkaloid. "( The inhibition of CYP enzymes in mouse and human liver by pilocarpine.
Alhava, E; Juvonen, RO; Kimonen, T; Pasanen, M, 1995
)
1.16
"Pilocarpine is a well established topical agent, but suffers troublesome sequelae, the most apparent of which is pupillary constriction."( The effect of pilocarpine on the glaucomatous visual field.
Canning, CR; Elkington, AR; Luff, AJ; Webster, AR, 1993
)
1.37
"The pilocarpine TDS is a new nonocular pharmaceutical device that should avoid the side effects well known in glaucoma treatment when conventional eye drops are used."( A new transdermal delivery system for pilocarpine in glaucoma treatment.
Diestelhorst, M; Dinslage, S; Hille, T; Otto, K, 1996
)
1.05
"Pilocarpine spray is an effective delivery modality for intraocular miosis."( Pilocarpine spray: an alternative delivery method.
Campagna, JA; Doe, EA, 1998
)
2.46
"Pilocarpine is a cholinergic agonist that increases salivary flow and has been used to treat xerostomia. "( Effect of pilocarpine mouthwash on salivary flow.
Barros, HM; Becker, FL; Bernardi, R; Gheno, GZ; Lopes, LR; Perin, C; Pires, M; Ramos, GZ, 2002
)
2.16
"Pilocarpine is a muscarinic agonist that readily crosses the blood-brain barrier and was therefore employed to examine both central and peripheral muscarinic mechanisms in modulating fetal cardiovascular function."( Central muscarinic modulation of fetal blood pressure and heart rate.
Hinman, DJ; Szeto, HH, 1990
)
1
"Pilocarpine which is a well-known partial agonist on muscarinic receptors in most smooth muscles did not cause any contraction in this tissue."( Muscarinic acetylcholine receptors in the rabbit ciliary body smooth muscle: spare receptors and threshold phenomenon.
Konno, F; Takayanagi, I, 1985
)
0.99
"Pilocarpine was judged to be an inadequate substitute for more physiological, gustatory stimuli."( The composition f human saliva secreted in response to a gustatory stimulus and to pilocaprine.
Dawes, C, 1966
)
0.97

Effects

Pilocarpine isosteres have been synthesized and characterized with regard to their in vitro muscarinic properties. The pilocarpin animal model has been broadly used to study the acute effects of seizures on neurogenesis.

ExcerptReferenceRelevance
"Pilocarpine isosteres have been synthesized and characterized with regard to their in vitro muscarinic properties. "( Muscarinic activity of the thiolactone, lactam, lactol, and thiolactol analogues of pilocarpine and a hypothetical model for the binding of agonists to the m1 receptor.
Amstutz, R; Boelsterli, J; Bolliger, G; Floersheim, P; Gammenthaler, H; Gmelin, G; Shapiro, G; Supavilai, P; Walkinshaw, M, 1992
)
1.95
"Oral pilocarpine has been shown to be effective treatment for radiation-induced xerostomia, although its usefulness is being discussed."( Safety and efficacy of oral pilocarpine in radiation-induced xerostomia in oropharyngeal carcinoma patients.
Kaur, H; Sandhu, SK; Singh Banipal, RP; Singh, H; Sonik, YA,
)
0.88
"The pilocarpine animal model has been broadly used to study the acute effects of seizures on neurogenesis and plasticity processes and the resulting epileptogenesis."( Effects of acute seizures on cell proliferation, synaptic plasticity and long-term behavior in adult zebrafish.
Budaszewski Pinto, C; Cagliari Zenki, K; Calcagnotto, ME; Dalmaz, C; de Sá Couto-Pereira, N; Kawa Odorcyk, F; Losch de Oliveira, D, 2021
)
1.1
"Pilocarpine has been shown to stimulate the secretion of saliva."( Pilocarpine and artificial saliva for the treatment of xerostomia and xerophthalmia in Sjögren syndrome: a double-blind randomized controlled trial.
Cifuentes, M; Del Barrio-Díaz, P; Vera-Kellet, C, 2018
)
2.64
"Pilocarpine has little effect on activity of MMP1/2. "( Impact of combination use of 0.004% travoprost and 2% pilocarpine on matrix metalloproteinases synthesized by rabbit ciliary muscle: a pilot study.
Zhang, SH; Zhao, JL, 2013
)
2.08
"The pilocarpine model of TLE has been widely used to study characteristics of human TLE, including behavioral comorbidities."( Evaluation of potential gender-related differences in behavioral and cognitive alterations following pilocarpine-induced status epilepticus in C57BL/6 mice.
Fighera, MR; Funck, VR; Furian, AF; Grigoletto, J; Oliveira, CV; Oliveira, MS; Ribeiro, LR; Royes, LF, 2015
)
1.11
"Pilocarpine has several important pharmaceutical applications."( Unraveling the biosynthesis of pilocarpine in Pilocarpus microphyllus.
Costa, YD; Mazzafera, P; Sawaya, AC, 2015
)
1.42
"Pilocarpine has been used widely in the treatment of dry mouth and glaucoma. "( Efficacy and safety of pilocarpine for radiation-induced xerostomia in patients with head and neck cancer: A systematic review and meta-analysis.
Cheng, CQ; Li, J; Liu, L; Liu, YT; Wang, RN; Xu, H; Zhou, XK, 2016
)
2.19
"The pilocarpine model has been recognized as an animal model of TLE."( Time course evaluation of behavioral impairments in the pilocarpine model of epilepsy.
Costa, AP; de Mello, N; Farina, M; Gonçalves, FM; Leal, RB; Lopes, MW; Lopes, SC; Prediger, RD; Santos, DB; Walz, R, 2016
)
1.16
"Pilocarpine has some efficacy in the treatment of xerostomia from radiation therapy, graft-versus-host disease and Sjögren's syndrome. "( Systemic pilocarpine for treatment of xerostomia.
Berk, L, 2008
)
2.21
"Pilocarpine has been widely used in ophthalmic preparations for the treatment of glaucoma and in oral preparations for the treatment of radiation-induced xerostomia and Sjögren syndrome. "( Human paraoxonase 1 is the enzyme responsible for pilocarpine hydrolysis.
Fukami, T; Hioki, T; Nakajima, M; Yokoi, T, 2011
)
2.07
"Pilocarpine has been approved for the treatment of this condition in the chronic phase, but its use concurrent with radiation could also be beneficial for prevention or reduction of the subsequent radiation-induced xerostomia."( A randomized, double-blind, placebo-controlled trial of concomitant pilocarpine with head and neck irradiation for prevention of radiation-induced xerostomia.
Haddad, P; Karimi, M, 2002
)
1.27
"Pilocarpine has been used as an ophthalmologic agent for decades; however, toxicity rarely has been reported in the medical literature. "( Pilocarpine toxicity and the treatment of xerostomia.
Greenberg, MI; Hendrickson, RG; Morocco, AP, 2004
)
3.21
"Pilocarpine hydrochloride has been reported to increase salivation and decrease oral mucositis in patients receiving head and neck radiotherapy, but there is only one report of its use in a cancer chemotherapy patient population. "( Randomized controlled trial of pilocarpine hydrochloride for the moderation of oral mucositis during autologous blood stem cell transplantation.
Brennan, MT; Fox, PC; Frenette, G; Kent, ML; Lockhart, PB; Norton, HJ; Packman, CH, 2005
)
2.06
"Pilocarpine has been approved for post-radiation xerostomia, and the effect of its use during radiation therapy on salivary flow, xerostomia, mucositis, and quality of life (QOL) was assessed in a phase III study conducted by the Radiation Therapy Oncology Group (RTOG 97-09)."( Effect of pilocarpine during radiation therapy: results of RTOG 97-09, a phase III randomized study in head and neck cancer patients.
Brachman, D; Foote, R; Hodson, DI; Lee, N; LeVeque, F; Meredith, R; Scarantino, C; Schulsinger, A; Swann, RS; White, R, 2006
)
1.46
"Pilocarpine has been used as a choice of drugs for treatment of impaired salivary flow. "( Effects of pilocarpine on the secretory acinar cells in human submandibular glands.
Choi, SY; Chung, SC; Kim, JS; Lee, JH; Lee, S; Lee, SJ; Li, J; Oh, SB; Park, K, 2006
)
2.17
"Pilocarpine preparations have been used since the 1870s, but the need to administer them frequently everyday has been unfavorable for many patients."( [A history of the development of eye drops used to treat glaucoma].
Komatsu, Y, 2007
)
1.06
"Pilocarpine has proved to be beneficial in the treatment of sialadenosis in bulimic patients."( Sialadenosis in bulimia. A new treatment.
Mehler, PS; Wallace, JA, 1993
)
1.73
"Pilocarpine has been well recognized as the drug of choice for acute angle-closure glaucoma. "( Anterior chamber angles shallowing and intraocular pressure after topical pilocarpine.
Chou, SC; Hung, L; Hung, PT; Tsai, CB; Yang, CC; Yang, CH, 1997
)
1.97
"Pilocarpine HCl has been shown to stimulate parotid and submandibular gland salivary flow. "( Oral pilocarpine HCl stimulates labial (minor) salivary gland flow in patients with Sjögren's syndrome.
Rhodus, NL, 1997
)
2.25
"As pilocarpine hydrochloride has been shown to relieve xerostomia in other disease categories, we administered pilocarpine hydrochloride 30 mg/day to six cGVHD patients and measured their whole saliva, parotid and submandibular-sublingual flow rates in both resting and stimulated conditions."( Pilocarpine hydrochloride relieves xerostomia in chronic graft-versus-host disease: a sialometrical study.
Nagler, A; Nagler, RM, 1999
)
2.26
"Pilocarpine has been used to lower intraocular pressure (IOP) in glaucoma patients for more than 100 years. "( Exploring the potential for subtype-selective muscarinic agonists in glaucoma.
Brann, M; Gil, D; Kharlamb, A; Li, D; Skjaerbaek, N; Spalding, T; Trotter, C; Uldam, A; Wheeler, L; WoldeMussie, E, 2001
)
1.75
"Pilocarpine HCl (Salagen) has been shown to be effective in increasing salivary flow in patients with SS."( An update on the management for the dental patient with Sjögren's syndrome and xerostomia.
Rhodus, NL,
)
0.85
"Pilocarpine test has been used since long to study the functional status of sweat glands. "( Pilocarpine test in assessment of therapeutic efficacy in maculoanaesthetic leprosy.
Joshi, PB, 1976
)
3.14

Actions

Pilocarpine appears to inhibit SO2-induced bronchoconstriction in nonasthmatic subjects, and this effect is not explained by an increase in airway tone. The drug did not inhibit the TRH-induced increase in PRL release when rats were first pre-treated with the dopamine receptor blocker, haloperidol.

ExcerptReferenceRelevance
"Pilocarpine induced an increase in intracellular Ca(2+) concentration in dispersed submandibular gland cells at 37 degrees C, but not 25 degrees C."( Pilocarpine-induced salivary fluid secretion in the perfused submandibular gland of the rat.
Murakami, M; Narita, T; Qi, B; Sugiya, H, 2009
)
2.52
"pilocarpine also did not produce significant difference with respect to the 0.4 mg pilocarpine group."( Arginine vasopressin does not contribute to seizures induced by intracerebroventricularly-injected pilocarpine.
Gulec, G; Isbil-Buyukcoskun, N, 2005
)
1.27
"Oral pilocarpine induced an increase in goblet cells number and an amelioration of conjunctival epithelium not dependent on tear secretion."( Conjunctival epithelium improvement after systemic pilocarpine in patients with Sjogren's syndrome.
Aragona, P; Di Pietro, R; Mobrici, M; Spinella, R, 2006
)
1.1
"Pilocarpine caused an increase of flare to 167 photon counts (pc)/ms at 7 hours, compared with the nontreated control eye mean value 3.7 pc/ms."( Effect of topically applied 2% pilocarpine and 0.25% demecarium bromide on blood-aqueous barrier permeability in dogs.
Krohne, SG, 1994
)
1.3
"Li-pilocarpine failed to activate most of the brainstem and the superior colliculus."( Mapping of cerebral metabolic activation in three models of cholinergic convulsions.
Jenden, DJ; Li, MG; Scremin, OU; Shih, TM, 1998
)
0.81
"Pilocarpine causes an increase in outflow facility which persists after cataract extraction and posterior chamber lens implantation."( Effect of cataract extraction and posterior chamber lens implantation on outflow facility and its response to pilocarpine in Korean subjects.
Kee, C; Moon, SH, 2000
)
1.24
"Pilocarpine did not inhibit Interleukin-2 (IL-2) production by human peripheral blood mononuclear cells but decreased the number of interleukin-2 receptor bearing cells (TAC positive cells)."( The inhibitory effect of the muscarinic agonist pilocarpine on lymphocyte activation involves the IL-2 pathway and the increase in suppressor cell function.
Arzt, E; Fernandez Castelo, S; Finkielman, S; Nahmod, V; Prync, AE, 1992
)
1.26
"Thus pilocarpine appears to inhibit SO2-induced bronchoconstriction in nonasthmatic subjects, and this effect is not explained by an increase in airway tone."( A muscarinic agonist inhibits reflex bronchoconstriction in normal but not in asthmatic subjects.
Barnes, PJ; Dixon, CM; Lammers, JW; McCusker, MT; Minette, PA, 1989
)
0.73
"Pilocarpine did not inhibit the TRH-induced increase in PRL release when rats were first pre-treated with the dopamine receptor blocker, haloperidol."( Effect of CNS-active drugs on TRH-induced prolactin release.
Forman, LJ; Hylka, VW; Meites, J; Sonntag, WE, 1986
)
0.99

Treatment

Pilocarpine, used in the treatment of glaucoma, shows basically parasympathomimetic activities. In contrast to choline derivatives an extremely potent effect on salivary and sweat glands and a noticeable increase of bronchial secretion.

ExcerptReferenceRelevance
"In pilocarpine-treated mice, mossy cell density and excitation of DGCs were reduced in parallel, with only a minimal reduction in feedforward inhibition, enhancing the inhibition/excitation ratio."( Adaptive Mossy Cell Circuit Plasticity after Status Epilepticus.
Butler, CR; Schnell, E; Westbrook, GL, 2022
)
1.24
"Pilocarpine treatment significantly restored the scopolamine-induced impaired recognition memory and downregulated hippocampal IEGs expression and phosphorylation of ERK1/2 (extracellular signal-regulated kinase 1/2) and CREB (cAMP response element-binding protein)."( Muscarinic Acetylcholine Receptors-Mediated Activation of PKC Restores the Hippocampal Immediate Early Gene Expression and CREB Phosphorylation in Scopolamine-Induced Amnesic Mice.
Barman, B; Kushwaha, A; Thakur, MK, 2022
)
1.44
"Pilocarpine (PILO) treatment was administered after the last day of treatment, and the epileptic behavior was recorded for 1 h and analyzed by an adapted scale."( Geniposide and asperuloside alter the COX-2 and GluN2B receptor expression after pilocarpine-induced seizures in mice.
da SilvaTorres, IL; de Oliveira, JDM; Medeiros, HR; Pereira, P; Pflüger, P; Picada, JN; Uczay, M; Vendruscolo, MH; von Poser, G, 2023
)
1.86
"Pilocarpine treatment (topical ± systemic) is an effective therapy for unilateral dry eye disease in cases suspected to be neurogenic in origin. "( A retrospective evaluation of systemic and/or topical pilocarpine treatment for canine neurogenic dry eye: 11 cases.
Wegg, ML, 2020
)
2.25
"Pilocarpine-treated neonatal rats showed long-term abnormal neurobehavioral parameters."( Alterations in the Neurobehavioral Phenotype and ZnT3/CB-D28k Expression in the Cerebral Cortex Following Lithium-Pilocarpine-Induced Status Epilepticus: the Ameliorative Effect of Leptin.
Chen, SH; Jin, MF; Li, LL; Ni, H, 2019
)
1.45
"Pilocarpine treatment reduced immobility time in forced swimming test but did not affect fear conditioning response, sucrose preference or novelty supressed feeding behaviour."( Enduring effects of muscarinic receptor activation on adult hippocampal neurogenesis, microRNA expression and behaviour.
Cryan, JF; Dinan, TG; Gururajan, A; Hoeller, AA; Levone, BR; Lino-de-Oliveira, C; Moloney, G; Monteiro de Lima, TC; O'Leary, OF; Ramos Costa, AP, 2019
)
1.24
"Pilocarpine (pilo)-treated mice housed together showed increased levels of anhedonia, anxiety and stress markers as well as decreased cognitive performance as compared to the control group."( Effects of Single Cage Housing on Stress, Cognitive, and Seizure Parameters in the Rat and Mouse Pilocarpine Models of Epilepsy.
Ba-M'hamed, S; Becker, C; Bennis, M; Benoliel, JJ; Bernard, C; Ghestem, A; Manouze, H; Poillerat, V,
)
1.07
"Pilocarpine treatment induced an increase of BDNF transcripts encoding exons 4 and 6 in all dendritic laminae and, additionally, of exon 2 in CA1 stratum radiatum and exons 2, 3, 9a in DG molecular layer while the other transcripts were decreased in dendrites, suggesting restriction to the soma."( Regulation of the spatial code for BDNF mRNA isoforms in the rat hippocampus following pilocarpine-treatment: a systematic analysis using laser microdissection and quantitative real-time PCR.
Baj, G; Del Turco, D; Deller, T; Schlaudraff, J; Tongiorgi, E; Torelli, L, 2013
)
1.33
"Pilocarpine treated rats that exhibited spontaneous seizures were implanted with drivable tetrodes including an LFP electrode and recordings were obtained from the CA3 region."( Neuronal synchrony and the transition to spontaneous seizures.
Grasse, DW; Karunakaran, S; Moxon, KA, 2013
)
1.11
"In pilocarpine-treated animals, β-AR-mediated LTP was strongly reduced in the distal subiculum."( Gating of hippocampal output by β-adrenergic receptor activation in the pilocarpine model of epilepsy.
Bartsch, JC; Behr, J; Gilling, KE; Grosser, S; Heinemann, U; Hollnagel, JO, 2015
)
1.16
"The pilocarpine-treated rats (n =21) exhibited (a) a decreased exploratory activity in comparison with control rats (n = 20) in the open field (OP) test and (b) a slower extinction of exploratory behavior in repeated OP tests."( Impairment of exploratory behavior and spatial memory in adolescent rats in lithium-pilocarpine model of temporal lobe epilepsy.
Frolova, EV; Kalemenev, SV; Kim, KKh; Lavrentyeva, VV; Lukomskaya, NY; Magazanik, LG; Sizov, VV; Zaitsev, AV; Zubareva, OE, 2015
)
1.12
"In pilocarpine-treated rats, DBS countered the significant increase in hippocampal caspase 3 activity and interleukin-6 (IL-6) levels that follows SE but had no effect on tumor necrosis factor α (TNFα)."( Deep brain stimulation induces antiapoptotic and anti-inflammatory effects in epileptic rats.
Amorim, BO; Brito, JG; Covolan, L; de Morais, DG; deAlmeida, AC; Ferreira, E; Hamani, C; Nobrega, JN; Nunes, DP; Rodrigues, AM, 2015
)
1.04
"In pilocarpine-treated chronically epileptic rats, we describe a novel mechanism that causes an increased proximal dendritic persistent Na(+) current (INaP)."( Downregulation of Spermine Augments Dendritic Persistent Sodium Currents and Synaptic Integration after Status Epilepticus.
Beck, H; Becker, A; Kaupp, UB; Kelly, T; Opitz, T; Otte, DM; Pitsch, J; Rennhack, A; Royeck, M; Schoch, S; Woitecki, A; Yaari, Y; Zimmer, A, 2015
)
0.93
"Pilocarpine treatment, like cpa6 knockdown, led to a reduced sensitivity to pentylenetetrazole when tested 1 day after pilocarpine treatment."( Knockdown of Carboxypeptidase A6 in Zebrafish Larvae Reduces Response to Seizure-Inducing Drugs and Causes Changes in the Level of mRNAs Encoding Signaling Molecules.
Fricker, LD; Leal, RB; Lopes, MW; Sapio, MR, 2016
)
1.16
"Pilocarpine-treated and control rats were sacrificed at different periods (24 h, 10 days, one month and more than two months) following SE."( Differential changes in mGlu2 and mGlu3 gene expression following pilocarpine-induced status epilepticus: a comparative real-time PCR analysis.
Arshadmansab, MF; Ermolinsky, B; Garrido-Sanabria, ER; Pacheco Otalora, LF; Zarei, MM, 2008
)
1.3
"Six pilocarpine-treated Wistar rats exhibiting spontaneous recurrent seizures and nine control rats were studied with PET using [(18)F]-fallypride, a high-affinity dopamine D(2/3) receptor ligand. "( In vivo imaging of dopamine receptors in a model of temporal lobe epilepsy.
Bartenstein, P; Buchholz, HG; Cumming, P; Debus, F; Dupont, E; Fellgiebel, A; Heimann, A; Landvogt, C; Luhmann, HJ; Potschka, H; Schreckenberger, M; Tillmanns, J; Werhahn, KJ; Yakushev, IY, 2010
)
0.92
"Pilocarpine treatment significantly reduced the GAP-43 immunoreactivity in the inner molecular layer in both species, with some minor differences in the staining pattern."( Comparative immunohistochemistry of synaptic markers in the rodent hippocampus in pilocarpine epilepsy.
Dobó, E; Károly, N; Mihály, A, 2011
)
1.32
"Pilocarpine treatment had no effect on the distribution of spines on dendrites of the collar Kenyon cells."( Muscarinic regulation of Kenyon cell dendritic arborizations in adult worker honey bees.
Dobrin, SE; Fahrbach, SE; Herlihy, JD; Robinson, GE, 2011
)
1.09
"In pilocarpine-treated mice, CCK was observed in dendritic spines and these were proportionally increased relative to controls, whereas the proportion of CCK-labeled terminals forming symmetric synapses was decreased."( Increased cholecystokinin labeling in the hippocampus of a mouse model of epilepsy maps to spines and glutamatergic terminals.
Houser, CR; Wyeth, MS; Zhang, N, 2012
)
0.89
"Pilocarpine-treated mice are an increasingly used model of temporal lobe epilepsy. "( Factors affecting outcomes of pilocarpine treatment in a mouse model of temporal lobe epilepsy.
Buckmaster, PS; Haney, MM, 2012
)
2.11
"In pilocarpine-treated animals, this long-term depression persisted in older animals, indicating impaired maturation of the dentate gyrus."( Impaired maturation of serotonergic function in the dentate gyrus associated with epilepsy.
Behr, J; Gilling, KE; Oltmanns, F, 2013
)
0.9
"Pilocarpine treatment induced downregulation of (M(1)+M(2)) muscarinic receptors and reduced the dissociation constants of (M(1)+M(2)) muscarinic and D(2) dopaminergic receptors, suggesting that these systems exert opposite effects on the regulation of convulsive activity."( Pilocarpine-induced seizures in adult rats: monoamine content and muscarinic and dopaminergic receptor changes in the striatum.
Bezerra Felipe, CF; Fonteles, MM; Freitas, RM; Nascimento, VS; Oliveira, AA; Viana, GS, 2003
)
2.48
"Pilocarpine-treated animals had significantly more BrdU-labeled DGCs than did littermate controls at all times. "( Fate of newborn dentate granule cells after early life status epilepticus.
Brooks-Kayal, AR; Maronski, M; Porter, BE, 2004
)
1.77
"Pilocarpine treatment dramatically increased saliva production but had no discernible effect on AQP-5 distribution."( Immunolocalization of AQP-5 in rat parotid and submandibular salivary glands after stimulation or inhibition of secretion in vivo.
Agre, P; Gong, H; Gresz, V; King, LS; Kwon, TH; Nielsen, S; Steward, MC, 2004
)
1.04
"Pilocarpine treatment induced down-regulation of GABAergic receptors in the hippocampus (38%), striatum (15%) and frontal cortex (11%)."( Pilocarpine-induced status epilepticus in rats: lipid peroxidation level, nitrite formation, GABAergic and glutamatergic receptor alterations in the hippocampus, striatum and frontal cortex.
Fonteles, MM; Freitas, RM; Sousa, FC; Vasconcelos, SM; Viana, GS, 2004
)
2.49
"In pilocarpine-treated animals, the normal diffuse labeling of the delta subunit in the dentate molecular layer was decreased by 4 d after status epilepticus (latent period) and remained low throughout the period of chronic seizures."( Altered expression of the delta subunit of the GABAA receptor in a mouse model of temporal lobe epilepsy.
Houser, CR; Huang, CS; Mody, I; Peng, Z; Stell, BM, 2004
)
0.84
"In pilocarpine-treated rats the subiculum showed cell loss of about 30%."( Cellular and network properties of the subiculum in the pilocarpine model of temporal lobe epilepsy.
Behr, J; Heinemann, U; Kivi, A; Knopp, A; Wozny, C, 2005
)
1.09
"In pilocarpine-treated rats, the mEC showed a moderate layer III cell loss and an enhanced susceptibility to epileptiform discharges compared to control animals."( Entorhinal cortex entrains epileptiform activity in CA1 in pilocarpine-treated rats.
Behr, J; Gabriel, S; Heinemann, U; Jandova, K; Schulze, K; Wozny, C, 2005
)
1.09
"Pilocarpine-treated male rats (60-70-day old) presented an enhancement in ectonucleotidase activities in the synaptosomes of the cerebral cortex (33, 40 and 64% for ATP, ADP and AMP hydrolysis, respectively) and hippocampus (55, 98 and 101% for ATP, ADP and AMP hydrolysis, respectively)."( Ontogenetic profile of ectonucleotidase activities from brain synaptosomes of pilocarpine-treated rats.
Bonan, CD; Bruno, AN; de Paula Cognato, G; Sarkis, JJ; Vuaden, FC, 2005
)
1.28
"Pilocarpine-treated animals represent an established model of mesial temporal lobe epilepsy."( Impaired activation of CA3 pyramidal neurons in the epileptic hippocampus.
Avoli, M; Baldelli, E; Biagini, G; D'Antuono, M; D'Arcangelo, G; Tancredi, V, 2005
)
1.05
"Pilocarpine treatment significantly improved global assessment of dry mouth, symptoms associated with dry mouth (mouth comfort, ability to sleep and ability to speak), and saliva production compared to placebo. "( Pilocarpine hydrochloride for the treatment of xerostomia in patients with Sjögren's syndrome in Taiwan--a double-blind, placebo-controlled trial.
Hsieh, SC; Lee, KL; Li, KJ; Lu, MC; Wu, CH; Yu, CL, 2006
)
3.22
"Pilocarpine pre-treated rats, protection of parotid gland function was seen in the early-intermediate phase (0-120 days) after 15 Gy and in the late phase (>120 days) after 10 and 15 Gy. "( Optimum dose range for the amelioration of long term radiation-induced hyposalivation using prophylactic pilocarpine treatment.
Burlage, FR; Coppes, RP; Faber, H; Kampinga, HH; Langendijk, JA; Roesink, JM; Vissink, A, 2008
)
2
"LiCl-pilocarpine-treated animals showed higher levels of S100B immunocontent in the CSF as well as a positive correlation between the score for sprouting and the GFAP immunocontent in the CA1 subfield, suggesting an astrocytic response to neuronal injury."( Effects of early-life LiCl-pilocarpine-induced status epilepticus on memory and anxiety in adult rats are associated with mossy fiber sprouting and elevated CSF S100B protein.
da Silva, MC; de Oliveira, DL; e Souza, TM; Fischer, A; Gonçalves, CA; Jorge, RS; Leite, M; Quillfeldt, JA; Souza, DO; Wofchuk, S, 2008
)
1.1
"Pilocarpine, used in the treatment of glaucoma, shows basically parasympathomimetic activities and in contrast to choline derivatives an extremely potent effect on salivary and sweat glands and a noticeable increase of bronchial secretion. "( [The effect of unintentional overdoses of pilocarpine on pulmonary surfactant in mice].
Curti, PC; Renovanz, HD, 1981
)
1.97
"Pilocarpine treatment caused an increase in N-acetylhexosamine concentration in the incubation fluid."( Effect of pilocarpine on behavior of mucus glycoproteins of canine tracheal secretory cells.
Misawa, M; Nishimura, T; Takeda, H; Yanaura, S, 1982
)
1.39
"Pilocarpine-treated membranes resulted in 19.9 +/- 7.5 mg of retrievable mucus as compared with 28.8 +/- 7.2 mg in controls (p < 0.05)."( Role of intestinal mucus in transepithelial passage of bacteria across the intact ileum in vitro.
Albanese, CT; Cardona, M; Kurkchubasche, AG; Rowe, MI; Simmons, RL; Smith, SD; Ulman, I; Watkins, S, 1994
)
1.01
"The pilocarpine-treated group had a lower frequency of oral symptoms during treatment than the placebo-treated group. "( Use of pilocarpine during head and neck radiation therapy to reduce xerostomia and salivary dysfunction.
Atkinson, JC; Fox, PC; Macynski, AA; Valdez, IH; Wolff, A, 1993
)
1.3
"In pilocarpine-treated rats, however, kappa receptor-mediated effects were seen in both ventral and more dorsal sections."( Spontaneous excitatory currents and kappa-opioid receptor inhibition in dentate gyrus are increased in the rat pilocarpine model of temporal lobe epilepsy.
Chavkin, C; Simmons, ML; Terman, GW, 1997
)
1.02
"In pilocarpine-treated animals an augmentation of rises in [K+]o was restricted to SP and its immediate vicinity."( Effects of barium on stimulus induced changes in extracellular potassium concentration in area CA1 of hippocampal slices from normal and pilocarpine-treated epileptic rats.
Eilers, A; Gabriel, S; Heinemann, U; Kivi, A; Kovacs, R; Lehmann, TN; Schulze, K, 1998
)
1.02
"The pilocarpine-treated animals displayed both ictal activity and interictal spikes on EEG analysis, whereas MK-801-pilocarpine and control animals only exhibited normal background EEG patterns."( NMDA receptor activation during status epilepticus is required for the development of epilepsy.
DeLorenzo, RJ; Rice, AC, 1998
)
0.78
"Pilocarpine-treated animals scored significantly higher on two of the behavioral tests: the Touch test and the Pick-Up test. "( Status epilepticus causes long-term NMDA receptor-dependent behavioral changes and cognitive deficits.
DeLorenzo, RJ; Floyd, CL; Hamm, RJ; Lyeth, BG; Rice, AC, 1998
)
1.74
"Pilocarpine-treated animals, which did not develop status epilepticus, showed no change in growth-associated phosphoprotein levels, indicating that status epilepticus is important to induce growth-associated phosphoprotein overexpression."( Growth-associated phosphoprotein expression is increased in the supragranular regions of the dentate gyrus following pilocarpine-induced seizures in rats.
Cavalheiro, EA; Funke, MG; Naffah-Mazzacoratti, MG; Sanabria, ER, 1999
)
1.23
"Pilocarpine-treated rats were studied because they not only have seizures and increased BDNF expression in granule cells, but they also have reorganization of granule cell "mossy fiber" axons."( Actions of brain-derived neurotrophic factor in slices from rats with spontaneous seizures and mossy fiber sprouting in the dentate gyrus.
Goodman, JH; Scharfman, HE; Sollas, AL, 1999
)
1.02
"Pilocarpine-treated rats present status epilepticus, which is followed by a seizure-free period (silent), by a period of spontaneous recurrent seizures (chronic), and the hippocampus of these animals exhibits cell loss and mossy fiber sprouting."( Selective alterations of glycosaminoglycans synthesis and proteoglycan expression in rat cortex and hippocampus in pilocarpine-induced epilepsy.
Amado, D; Argañaraz, GA; Bellissimo, MI; Cavalheiro, EA; Nader, HB; Naffah-Mazzacoratti, MG; Porcionatto, MA; Scorza, FA; Silva, R, 1999
)
1.23
"In pilocarpine-treated casiraguas, stereological cell counts in Nissl-stained sections did not reveal significant neuronal loss in hippocampal subfields, where the examined markers exhibited instead striking changes."( The spiny rat Proechimys guyannensis as model of resistance to epilepsy: chemical characterization of hippocampal cell populations and pilocarpine-induced changes.
Bentivoglio, M; Carvalho, RA; Cavalheiro, EA; Correia, L; Fabene, PF, 2001
)
1.03
"Pilocarpine (25 mg/kg) pretreatment also predisposed to status epilepticus in response to the focal application of bicuculline, but diazepam (5 or 10 mg/kg i.p.) was ineffective in suppressing the status epilepticus in the presence of pilocarpine."( A rodent model of focally evoked self-sustaining status epilepticus.
Gale, K; Pazos, A; Peterson, CJ; Vinayak, S, 1992
)
1
"Pilocarpine pretreatment was protective against irradiation, displaying much less damage after irradiation of the same dosage, and with complete recovery after 4 weeks."( The effect of pilocarpine and atropine administration on radiation-induced injury of rat submandibular glands.
Kim, CW; Kim, JY; Kim, KH; Sung, MW, 1991
)
1.36
"Pilocarpine treatment was not associated with noticeable changes in intraocular inflammatory response, nor were significant ocular or systemic adverse reactions observed."( Management of increased intraocular pressure after cataract extraction.
Musgrove, KH; Prager, TC; Ruiz, RS; Wilson, CA, 1987
)
0.99
"Pretreatment of pilocarpine attenuated glutamate-induced neurotoxicity of primary retinal neurons in a dose-dependent manner. "( Activation of muscarinic receptors protects against retinal neurons damage and optic nerve degeneration in vitro and in vivo models.
Chen, HZ; Cui, YY; Feng, XM; Li, H; Qiu, Y; Tan, PP; Yuan, HH; Zhou, W; Zhu, X, 2014
)
0.75
"Eyes treated with pilocarpine developed approximately 6D myopia (p < 0.001 from 0 to 90 min) with a decrease in anterior lens radius of curvature (ALRC) (p < 0.001 from 0 to 90 min, repeated measures anova). "( Effects of muscarinic receptor modulators on ocular biometry of guinea pigs.
Fang, F; Huang, F; Li, C; Liu, Y; Qu, J; Xie, R; Zhou, X; Zhu, Y, 2015
)
0.75
"Treatment with pilocarpine (PILO) induces variable degrees of loss of mossy cells (MCs) and mossy fibre (MF) sprouting in rodents, the relationships of which have not been examined in individual animals. "( Comparative immunohistochemical study of the effects of pilocarpine on the mossy cells, mossy fibres and inhibitory neurones in murine dentate gyrus.
Dobó, E; Károly, N; Mihály, A, 2015
)
1.02
"Sham-treated pilocarpine rats but not sunitinib-treated pilocarpine rats had significantly smaller hippocampi."( Does angiogenesis play a role in the establishment of mesial temporal lobe epilepsy?
Avoli, M; Benini, R; Khoja, Z; Roth, R; Wintermark, P, 2016
)
0.79
"Mice treated with pilocarpine (n=24) presented 100% of mortality during the first hour of observation."( Anticonvulsant effect of phytol in a pilocarpine model in mice.
Costa, JP; De Sousa, DP; Ferreira, PB; Freitas, RM; Jordan, J, 2012
)
0.98
"Rats treated with pilocarpine (20 to 350 mg/kg, i.p.) that did not develop status epilepticus or spontaneous recurrent seizures were evaluated 1 month later in the elevated plus maze (EPM), T-maze (ETM), open-field (OF), and step-down avoidance tests. "( Anxiogenic-like profile of Wistar adult rats based on the pilocarpine model: an animal model for trait anxiety?
Carobrez, AP; De Lima, TC; Duarte, FS; Duzzioni, M; Ern, AL; Gavioli, EC; Hoeller, AA; Lemos, T; Piermartiri, TC; Silva, NM; Tasca, CI, 2013
)
0.97
"The treatment with pilocarpine improved in a specific manner these age-related deficits in 24 month-old rats without altering their motor performance."( Pilocarpine improves olfactory discrimination and social recognition memory deficits in 24 month-old rats.
De-Mello, N; Prediger, RD; Takahashi, RN, 2006
)
2.1
"Treatment with pilocarpine hydrochloride may be beneficial in the case of impaired salivary function in patients treated with radioiodine."( Pilocarpine for the treatment of salivary glands' impairment caused by radioiodine therapy for thyroid cancer.
Aframian, DJ; Helcer, M; Livni, D; Markitziu, A, 2006
)
2.13
"Pre -treatment with pilocarpine decreased the four proteins expression, which were increased by dexamethasone."( Molecular mechanism of bovine trabecular meshwork cells apoptosis induced by dexamethasone and protection by pilocarpine.
Gu, Y; Peng, D; Qiu, P; Wu, Y; Yan, G; Zeng, S, 2005
)
0.86
"Treatment with pilocarpine hydrochloride tablets may improve saliva secretion in patients taking xerogenic medications and/or suffering from metabolic sialosis expanding the beneficial potential of this sialogogue."( Pilocarpine treatment in a mixed cohort of xerostomic patients.
Aframian, DJ; Helcer, M; Livni, D; Markitziu, A; Nadler, C; Robinson, SD, 2007
)
2.14
"Pretreatment of pilocarpine could prevent glutamate-induced neuron death, which was blocked by the non-selective antagonist atropine and the M1-selective muscarinic receptor antagonist pirenzepine."( Neuroprotection of muscarinic receptor agonist pilocarpine against glutamate-induced apoptosis in retinal neurons.
Chen, HZ; Cui, YY; Qi, H; Ren, QS; Wang, H; Zhou, W; Zhu, L; Zhu, X, 2008
)
0.94
"A pretreatment with pilocarpine (1-100 microM) significantly reduced, while methoctramine (1-100 microM) significantly increased contraction induced by EFS."( Effects of neuraminidase on equine isolated bronchi.
Calzetta, L; Cazzola, M; Matera, MG; Page, CP; Sanduzzi, A, 2008
)
0.66
"Pretreatment with pilocarpine accelerated the release of amylase into the blood."( Transport to the bloodstream of amylase following retrograde infusion of amylase into the parotid glands in the rat.
Ikeno, K; Ikeno, T; Kuzuya, H, 1984
)
0.59
"Pre-treatment with pilocarpine eyedrops could be reduce the laser-mediated IOP rise to less than one fourth."( The immediate IOP response of Nd-YAG-laser iridotomy and its prophylactic treatability.
Eichelbrönner, O; Krieglstein, GK; Schrems, W, 1984
)
0.59
"Treatment with pilocarpine (30 mg/kg) alone increased mRNA levels in the order of c-fos > jun-B > c-jun but did not change the jun-D mRNA level, and maximal c-fos and jun-B mRNA levels occurred earlier (30 min) in the cortex than in the hippocampus."( Distinctive rat brain immediate early gene responses to seizures induced by lithium plus pilocarpine.
Jope, RS; Williams, MB, 1994
)
0.85
"Pretreatment with pilocarpine or methacholine resulted in an improvement of all measured functions of both glands. "( Muscarinic receptor stimulation increases tolerance of rat salivary gland function to radiation damage.
Coppes, RP; Konings, AW; Vissink, A; Zeilstra, LJ, 1997
)
0.63
"Treatment with pilocarpine (5 mg/kg, daily for 7 days) increased amylase release induced by isoproterenol (10(-5) M) or forskolin (10(-5) M) in the parotid tissue of rats after the removal of a 7-day-duct ligation."( Effect of isoproterenol and forskolin on amylase release from parotid tissue after chronic pilocarpine administration in rats following ligation removal.
Murata, K; Ogura, Y, 1987
)
0.83
"Eyes treated with pilocarpine gel had an average intraocular pressure increase of 4.2 +/- 2.1 mm Hg (mean +/- 1 S.E.), eyes treated with pilocarpine 4% eyedrops had an average increase of 9.8 +/- 2.8 mm Hg, and eyes treated with timolol demonstrated an intraocular pressure increase of 8.25 +/- 3.19."( Management of increased intraocular pressure after cataract extraction.
Musgrove, KH; Prager, TC; Ruiz, RS; Wilson, CA, 1987
)
0.6
"Treatment with Pilocarpine-induced myosis only worsened the glaucoma by causing a severe pupillary block."( Weill-Marchesani syndrome with bilateral angle-closure glaucoma.
Chrousos, GA; Wright, KW,
)
0.47

Toxicity

Pilocarpine was toxic to retinal ganglion cells in a dose-dependent fashion. The combination was well tolerated, and the adverse effects observed were consistent. Monotherapy with xalathane is safe sufficiently effective.

ExcerptReferenceRelevance
" The drug was well tolerated and without serious adverse effects."( [Efficacy and safety of long-term maintenance treatment with timolol ophthalmic solution in chronic open-angle glaucoma (author's transl)].
Katz, IM, 1979
)
0.26
" The toxic effect of pilocarpine gel on the corneal endothelium was much less than the effect produced with pilocarpine drops."( The toxic effects of pilocarpine gel and drops on rabbit cornea.
Basu, PK; Liu, GS; Trope, GE, 1989
)
0.91
" Possible implications for the therapeutic mechanisms and adverse effects of Li are considered."( Studies on the role of brain cholinergic systems in the therapeutic mechanisms and adverse effects of ECT and lithium.
Lerer, B, 1985
)
0.27
"Pilocarpine, a parasympathomimetic drug used in the treatment of glaucoma, produces a variety of ocular and systemic adverse reactions."( Miotics: side effects and ways to avoid them.
Wheeler, TM; Zimmerman, TJ, 1982
)
1.71
" Adverse event were reported by 70 out of 89 patients by the end of 2 weeks, but were severe enough only in 11 for the treatment to be discontinued."( Efficacy and safety of timolol/pilocarpine combination drops in glaucoma patients.
Palkama, A; Uusitalo, RJ, 1994
)
0.57
" Adverse experiences were those expected for a cholinergic agonist, with the most common being mild to moderate sweating."( Oral pilocarpine for radiation-induced xerostomia: integrated efficacy and safety results from two prospective randomized clinical trials.
Gallagher, SC; Hafermann, MD; Iwamoto, R; Johnson, JT; LeVeque, FG; Muscoplat, C; Rieke, JW; Steiger, BW, 1995
)
0.81
" The incidence of most adverse events increased with dose."( Oral pilocarpine for radiation-induced xerostomia: integrated efficacy and safety results from two prospective randomized clinical trials.
Gallagher, SC; Hafermann, MD; Iwamoto, R; Johnson, JT; LeVeque, FG; Muscoplat, C; Rieke, JW; Steiger, BW, 1995
)
0.81
"In patients requiring more than one ocular hypotensive agent, the combination of betaxolol and pilocarpine in a single formulation appears to be an effective and relatively safe agent."( Ocular hypotensive efficacy and safety of a combined formulation of betaxolol and pilocarpine.
Robin, AL, 1996
)
0.74
" Monotherapy with xalathane is safe sufficiently effective, and comparable to combined therapy with timolol and pilocarpine."( [Xalathane: comparative assessment of efficacy and safety in hypotensive therapy of glaucoma].
Erichev, VP; Iakubova, LV,
)
0.34
" The incidence of the most common drug-related adverse experiences in the first year was compared with that in the second year using McNemar's test."( Two-year safety study of dorzolamide as monotherapy and with timolol and pilocarpine. Dorzolamide Safety Study Group.
Adamsons, IA; Boyle, JE; Ostrov, CS; Polis, A, 1998
)
0.53
" Of the patients who received dorzolamide as monotherapy, drug-related adverse events occurred more frequently during the first year (29."( Two-year safety study of dorzolamide as monotherapy and with timolol and pilocarpine. Dorzolamide Safety Study Group.
Adamsons, IA; Boyle, JE; Ostrov, CS; Polis, A, 1998
)
0.53
" Drug-related adverse events were less frequent during the second year of monotherapy than during the first year."( Two-year safety study of dorzolamide as monotherapy and with timolol and pilocarpine. Dorzolamide Safety Study Group.
Adamsons, IA; Boyle, JE; Ostrov, CS; Polis, A, 1998
)
0.53
" It was therefore investigated whether pilocarpine was also toxic to retinal ganglion cells."( Pilocarpine toxicity in retinal ganglion cells.
Dreyer, EB; Gorla, M; Katowitz, W; Levin, LA; Simon, P; Vorwerk, CK; Zurakowski, D, 1999
)
2.02
"Pilocarpine was toxic to retinal ganglion cells in a dose-dependent fashion."( Pilocarpine toxicity in retinal ganglion cells.
Dreyer, EB; Gorla, M; Katowitz, W; Levin, LA; Simon, P; Vorwerk, CK; Zurakowski, D, 1999
)
3.19
"Pilocarpine is toxic to retinal ganglion cells in a mixed culture assay."( Pilocarpine toxicity in retinal ganglion cells.
Dreyer, EB; Gorla, M; Katowitz, W; Levin, LA; Simon, P; Vorwerk, CK; Zurakowski, D, 1999
)
3.19
"From this preliminary study, immediate paracentesis seems to be safe and effective in controlling the intraocular pressure and eliminating symptoms in acute PACG."( Efficacy and safety of immediate anterior chamber paracentesis in the treatment of acute primary angle-closure glaucoma: a pilot study.
Chua, JK; Lai, JS; Lam, DS; Tham, CC, 2002
)
0.31
"25% drops in twice daily dosage and does not result in any significant ocular and systemic adverse effects."( A prospective, long-term, randomized study of the efficacy and safety of the drug combination pilocarpine 1% with clonidine 0.06% or clonidine 0.125% versus timolol 0.25%.
Agarwal, H; Rajashekhar, YL; Sihota, R; Venkatesh, P, 2002
)
0.53
" Interestingly, oligohydrosis was found to be a relatively common side effect of zonisamide."( Oligohydrosis and hyperthermia: pilot study of a novel topiramate adverse effect.
Augarten, A; Ben-Zeev, B; Blatt, I; Brand, N; Efrati, O; Topper, L; Watemberg, N; Yahav, Y, 2003
)
0.32
"5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects."( Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
Benz, RD; Contrera, JF; Kruhlak, NL; Matthews, EJ; Weaver, JL, 2004
)
0.32
" pilocarpine for at least for 12 weeks unless they had experienced unacceptable adverse effects."( Oral pilocarpine (5mg t.i.d.) used for xerostomia causes adverse effects in Japanese.
Asakage, T; Ebihara, Y; Igaki, H; Nakagawa, K; Nakamura, N; Nakao, K; Ohtomo, K; Sasano, N; Shiraishi, K; Terahara, A; Yamashita, H, 2009
)
1.78
" The most common adverse effect was sweating with an incidence of 64%."( Oral pilocarpine (5mg t.i.d.) used for xerostomia causes adverse effects in Japanese.
Asakage, T; Ebihara, Y; Igaki, H; Nakagawa, K; Nakamura, N; Nakao, K; Ohtomo, K; Sasano, N; Shiraishi, K; Terahara, A; Yamashita, H, 2009
)
0.87
" pilocarpine caused a high incidence of unacceptable adverse effects."( Oral pilocarpine (5mg t.i.d.) used for xerostomia causes adverse effects in Japanese.
Asakage, T; Ebihara, Y; Igaki, H; Nakagawa, K; Nakamura, N; Nakao, K; Ohtomo, K; Sasano, N; Shiraishi, K; Terahara, A; Yamashita, H, 2009
)
1.78
" However, there is no drug that is safe and effective for the xerostomia that occurs in patients of this age group."( Efficacy and safety of orally administered pilocarpine hydrochloride for patients with juvenile-onset Sjögren's syndrome.
Kohno, Y; Kuwada, N; Nonaka, Y; Saito, K; Shimojo, N; Takei, S; Tomiita, M, 2010
)
0.62
" An understanding of structure-activity relationships (SARs) of chemicals can make a significant contribution to the identification of potential toxic effects early in the drug development process and aid in avoiding such problems."( Developing structure-activity relationships for the prediction of hepatotoxicity.
Fisk, L; Greene, N; Naven, RT; Note, RR; Patel, ML; Pelletier, DJ, 2010
)
0.36
" No serious adverse event was found in both the groups."( A 12-week, double-masked, parallel-group study of the safety and efficacy of travoprost 0.004% compared with pilocarpine 1% in Chinese patients with primary angle-closure and primary angle-closure glaucoma.
Gao, YX; Huang, P; Li, B; Wang, ZX; Wu, LL, 2011
)
0.58
"004% once daily is safe and well tolerated in PAC or PACG patients."( A 12-week, double-masked, parallel-group study of the safety and efficacy of travoprost 0.004% compared with pilocarpine 1% in Chinese patients with primary angle-closure and primary angle-closure glaucoma.
Gao, YX; Huang, P; Li, B; Wang, ZX; Wu, LL, 2011
)
0.58
" The combination was well tolerated, and the adverse effects observed were consistent with the known safety profiles of tolterodine and pilocarpine."( Clinical safety, tolerability and efficacy of combination tolterodine/pilocarpine in patients with overactive bladder.
Dmochowski, RR; Duchin, K; Paborji, M; Staskin, DR; Tremblay, TM, 2014
)
0.84
" Pilocarpine tablet ingestion can relieve dry mouth symptoms, but produces numerous adverse effects."( Efficacy and safety of pilocarpine mouthwash in elderly patients with xerostomia.
Sasaki, H; Sato, T; Shibata, R; Shinohara, A; Tanigawa, T; Ueda, H; Yamashita, J,
)
1.35
" Patients recorded all adverse effects."( Efficacy and safety of pilocarpine mouthwash in elderly patients with xerostomia.
Sasaki, H; Sato, T; Shibata, R; Shinohara, A; Tanigawa, T; Ueda, H; Yamashita, J,
)
0.44
" Adverse events were other outcomes of interest."( Efficacy and safety of pilocarpine for radiation-induced xerostomia in patients with head and neck cancer: A systematic review and meta-analysis.
Cheng, CQ; Li, J; Liu, L; Liu, YT; Wang, RN; Xu, H; Zhou, XK, 2016
)
0.74
" The aim of this investigation was to retrospectively run a head-to-head comparison for their effectiveness and frequency of adverse effects in patients with hyposalivation."( Comparing the effectiveness and adverse effects of pilocarpine and cevimeline in patients with hyposalivation.
Cimmino, J; Farag, AM; Holliday, C; Papas, A; Roomian, T, 2019
)
0.77
" The use of PILO was associated with a higher proportion of adverse effects compared to CEV (p = ."( Comparing the effectiveness and adverse effects of pilocarpine and cevimeline in patients with hyposalivation.
Cimmino, J; Farag, AM; Holliday, C; Papas, A; Roomian, T, 2019
)
0.77
" SjS is a relatively rare immune-related adverse event that might sometimes be overlooked."( Sjögren's Syndrome as an Immune-related Adverse Event of Nivolumab Treatment for Gastric Cancer.
Furuta, Y; Higashi, T; Miyamoto, H; Nagaoka, K; Naito, H; Nakayama, H; Naoe, H; Tanaka, M; Yoshida, R, 2020
)
0.56
" Safety measures included adverse events."( Safety and Efficacy of AGN-190584 in Individuals With Presbyopia: The GEMINI 1 Phase 3 Randomized Clinical Trial.
Gore, A; Guo, Q; Liu, H; McCabe, C; Moshirfar, M; Price, FW; Robinson, MR; Safyan, E; Waring, GO; Wirta, D, 2022
)
0.72
" AGN-190584 is a safe and efficacious topical therapy for presbyopia through 30 days."( Safety and Efficacy of AGN-190584 in Individuals With Presbyopia: The GEMINI 1 Phase 3 Randomized Clinical Trial.
Gore, A; Guo, Q; Liu, H; McCabe, C; Moshirfar, M; Price, FW; Robinson, MR; Safyan, E; Waring, GO; Wirta, D, 2022
)
0.72
" In addition, its richness in bioactive compounds gives it an antioxidant potential, and it is not toxic in acute and sub-acute toxicity."( Revealing the most effective anticonvulsant part of Malvaviscus arboreus Dill. Ex Cav. and its acute and sub-acute toxicity.
Adassi, MB; Foutsop, AF; Kom, TD; Ngo Bum, E; Ngoupaye, GT; Yassi, FB, 2023
)
0.91
" Key safety measures included treatment-emergent adverse events (TEAEs) and some ocular measurements."( Safety and Efficacy of Twice-Daily Pilocarpine HCl in Presbyopia: The Virgo Phase 3, Randomized, Double-Masked, Controlled Study.
El-Harazi, SM; Kannarr, S; Kim, JL; Lievens, C; Liu, H; Moshirfar, M; Peace, JH; Robinson, MR; Safyan, E; Zheng, S, 2023
)
1.19
" Adverse effects due to xerostomia were generally mild and occasionally of moderate severity."( Safety and efficacy of oral pilocarpine in radiation-induced xerostomia in oropharyngeal carcinoma patients.
Kaur, H; Sandhu, SK; Singh Banipal, RP; Singh, H; Sonik, YA,
)
0.43

Pharmacokinetics

The pharmacokinetic parameters of pilocarpi were observed. A gamma scintigraphic study has been carried out on the precorneal residence and pharmacodynamic action of a radiolabelled New Ophthalmic Delivery System (NODS)

ExcerptReferenceRelevance
"A pharmacokinetic model that permits prediction of aqueous humor pilocarpine levels following topical application to rabbit eyes was developed."( Preliminary pharmacokinetic model of pilocarpine uptake and distribution in the eye.
Guvenir, I; Himmelstein, KJ; Patton, TF, 1978
)
0.77
"By simplifying a pharmacokinetic treatment, an equation can be derived which predicts that equal areas under aqueous humor concentration-time profiles can be obtained by administering a dose to infants which is some fraction of the normal adult dose."( Pediatric dosing considerations in ophthalmology--dosage adjustments based on aqueous humor volume ratio.
Patton, TF,
)
0.13
" A gamma scintigraphic study has been carried out on the precorneal residence and pharmacodynamic action of a radiolabelled New Ophthalmic Delivery System (NODS) containing pilocarpine nitrate in 12 healthy volunteers."( Scintigraphic studies on the corneal residence of a New Ophthalmic Delivery System (NODS): rate of clearance of a soluble marker in relation to duration of pharmacological action of pilocarpine.
Bentley, PH; Birmingham, AT; Greaves, JL; Richardson, MC; Wilson, CG, 1992
)
0.67
" Pharmacokinetic analysis via the two-compartment open model showed that bile duct ligation caused a decrease in overall clearance from approximately 61."( Pharmacokinetics of procainamide in rats with extrahepatic biliary obstruction.
Basseches, PJ; DiGregorio, GJ, 1982
)
0.26
" Pharmacodynamic effects such as miosis and IOP reduction were investigated."( Pharmacokinetic and pharmacodynamic aspects of an ophthalmic pilocarpine nanoparticle-delivery-system.
Kreuter, J; Lambrecht, G; Mayer, D; Mutschler, E; Zimmer, A, 1994
)
0.53
"5 mg, dose-independent pharmacokinetic parameters included a small steady-state volume of distribution (2."( A pharmacokinetic and pharmacodynamic study of intravenous pilocarpine in humans.
Kramer, PA; Schulman, P; Tanzer, JM; Willard, AK, 1995
)
0.53
" Cmax and AUC were normalized to a 5 mg exposure in those subjects who received doses other than 5 mg."( Pharmacokinetics of pilocarpine in subjects with varying degrees of renal function.
Andersen, SA; Gallagher, SC; Gunderson, BW; Lambrecht, LJ; St Peter, JV; Swan, SK, 2000
)
0.63
"5%) containing sodium hyaluronate significantly increased the peak concentration of pilocarpine, shortened the time of reaching peak concentration and prolonged the half-life in aqueous humor."( [Ocular pharmacokinetics of 0.5% pilocarpine with sodium hyaluronate in rabbits].
Chen, ZJ; Lü, XF; Pang, GR; Song, JZ; Xu, Y; Zhang, JJ, 2004
)
0.83
" Simultaneously, the effects on hippocampal monoamines were studied as pharmacodynamic markers for the anticonvulsant activity."( Quantitative in vivo microdialysis study on the influence of multidrug transporters on the blood-brain barrier passage of oxcarbazepine: concomitant use of hippocampal monoamines as pharmacodynamic markers for the anticonvulsant activity.
Clinckers, R; Ebinger, G; Meurs, A; Michotte, Y; Smolders, I, 2005
)
0.33
"The pharmacokinetic parameters of pilocarpine, pilocarpic acid, and 3-hydroxypilocarpine after oral administration of pilocarpine hydrochloride in 28 Japanese participants were calculated based on the data obtained from two phase-1 clinical studies."( Genetic polymorphisms of CYP2A6 affect the in-vivo pharmacokinetics of pilocarpine.
Endo, T; Fukami, T; Hara, Y; Hasunuma, T; Momose, Y; Nakajima, M; Yokoi, T, 2008
)
0.86
"Relatively large interindividual differences were observed in the pharmacokinetic parameters of pilocarpine, pilocarpic acid, and 3-hydroxypilocarpine."( Genetic polymorphisms of CYP2A6 affect the in-vivo pharmacokinetics of pilocarpine.
Endo, T; Fukami, T; Hara, Y; Hasunuma, T; Momose, Y; Nakajima, M; Yokoi, T, 2008
)
0.8
" It seems that both anticonvulsant effect exerted by riluzole and proconvulsant effect exerted by topiramate in pilocarpine model of seizures are due to a pharmacokinetic interaction."( Evidences for pharmacokinetic interaction of riluzole and topiramate with pilocarpine in pilocarpine-induced seizures in rats.
Brzana, W; Czuczwar, M; Kiś, J; Nieoczym, D; Turski, WA; Wlaź, P; Zgrajka, W, 2010
)
0.8
" The objective of this study was to determine the pharmacokinetic parameters of tramadol and its primary metabolite, O-desmethyltramadol (M1), after oral administration of tramadol hydrochloride (HCl) in African penguins (Spheniscus demersus)."( Pharmacokinetics of tramadol and its primary metabolite O-desmethyltramadol in African penguins (Spheniscus demersus).
Bronson, E; Cox, SK; Kilburn, JJ; Kottyan, J; Wack, AN, 2014
)
0.4
" To elucidate the critical value of delivering drugs in solution onto the eyeball through the eyelid skin, pharmacokinetic studies of pilocarpine were conducted, and the results were verified using a direct pharmacodynamic study in rats."( Pharmacokinetics and Tissue Distribution of Pilocarpine After Application to Eyelid Skin of Rats.
Sagesaka, A; See, GL; Sugibayashi, K; Todo, H; Wierzba, K, 2019
)
0.98

Compound-Compound Interactions

54 patients with bilateral primary open angle glaucoma and comparable IOP were assigned to three study groups. The aim of the study was to conduct an in vivo evaluation of the relationship between treatments with synthetic cannabinoid arachidonyl-2'-chloroethylamide (ACEA) and hippocampus neurogenesis.

ExcerptReferenceRelevance
"We compared in two controlled studies the effect of pilocarpine 1% with the effect of pilocarpine 1% combined with 0,05% or 0,1% dipivalyl-epinephrine in patients with open-angle glaucoma."( [The pressure reducing effects of pilocarpin in combination with Dipivalyl-epinephrine in glaucoma simplex (author's transl)].
Krieglstein, GK; Leydhecker, W, 1979
)
0.51
"Topically applied 4% timolol, 4% timolol combined with 2% pilocarpine, 6% timolol, and 6% timolol combined with 2% pilocarpine were evaluated in clinically normal Beagles and Beagles with glaucoma."( Evaluation of multiple doses of 4 and 6% timolol, and timolol combined with 2% pilocarpine in clinically normal beagles and beagles with glaucoma.
Gelatt, JK; Gelatt, KN; Larocca, RD; MacKay, EO; Strubbe, DT, 1995
)
0.76
" Other antiglaucoma medications were administered with verapamil to determine their combined effect on intraocular pressure."( Effect of calcium channel blockers alone and in combination with antiglaucoma medications on intraocular pressure in the primate eye.
Erickson, KA; Netland, PA; Schroeder, A; Siegner, SW, 2000
)
0.31
"To evaluate the effects of high-frequency electrical stimulation (HFS) in both ventral hippocampi, alone and combined with a subeffective dose of antiepileptic drugs, during the status epilepticus (SE) induced by lithium-pilocarpine (LP)."( Antiepileptic drugs combined with high-frequency electrical stimulation in the ventral hippocampus modify pilocarpine-induced status epilepticus in rats.
Alcantara-Gonzalez, D; Cuellar-Herrera, M; Neri-Bazan, L; Peña, F; Rocha, L, 2010
)
0.76
" One minute following pilocarpine injection, HFS (pulses of 60 mus width at 130 Hz at subthreshold intensities and applied during 3 h) was applied alone or combined with subeffective doses of antiepileptic drugs."( Antiepileptic drugs combined with high-frequency electrical stimulation in the ventral hippocampus modify pilocarpine-induced status epilepticus in rats.
Alcantara-Gonzalez, D; Cuellar-Herrera, M; Neri-Bazan, L; Peña, F; Rocha, L, 2010
)
0.89
" This effect was not evident when HFS was combined with phenytoin (33."( Antiepileptic drugs combined with high-frequency electrical stimulation in the ventral hippocampus modify pilocarpine-induced status epilepticus in rats.
Alcantara-Gonzalez, D; Cuellar-Herrera, M; Neri-Bazan, L; Peña, F; Rocha, L, 2010
)
0.57
" The aim of the study was to conduct an in vivo evaluation of the relationship between treatments with synthetic cannabinoid arachidonyl-2'-chloroethylamide (ACEA) alone or in combination with valproic acid (VPA) and hippocampal neurogenesis in a mouse pilocarpine model of epilepsy."( A Long-Term Treatment with Arachidonyl-2'-Chloroethylamide Combined with Valproate Increases Neurogenesis in a Mouse Pilocarpine Model of Epilepsy.
Andres-Mach, M; Dudra-Jastrzębska, M; Haratym, J; Haratym-Maj, A; Maj, M; Rola, R; Zagaja, M; Łuszczki, JJ, 2017
)
0.84
" Therefore, in the present study, the neuroprotective effects and mechanisms of vit-D alone or in combination with lamotrigine have been evaluated in the lithium-pilocarpine model of SE in rats."( Neuroprotective effects of vitamin D alone or in combination with lamotrigine against lithium-pilocarpine model of status epilepticus in rats.
Abdel-Wahab, AF; Afify, MA; Al Ghamdi, SS; Bamagous, GA; ElSawy, NA; Ibrahim, IAA; Mahfoz, AM; Shahzad, N, 2017
)
0.87

Bioavailability

There was a two-fold increase in ocular bioavailability of pilocarpine due to the therapy with micron emulsion. In-vivo miosis vs time experiments on albino rabbits, showed that all in were effective.

ExcerptReferenceRelevance
" The extensive parallel elimination at the absorption site gives rise to an apparent absorption rate constant that is one to two orders of magnitude larger than the true absorption rate constant."( Pharmacokinetics of topically applied pilocarpine in the albino rabbit eye.
Makoid, MC; Robinson, JR, 1979
)
0.53
"The low ocular bioavailability of topically applied pilocarpine is attributed to extensive precorneal drug loss in conjection with the resistance to corneal penetration."( Mechanistic and quantitative evaluation of precorneal pilocarpine disposition in albino rabbits.
Lee, VH; Robinson, JR, 1979
)
0.76
"We used 20-day-old rabbits as a model to show that the ocular bioavailability of topically applied pilocarpine nitrate increased as the instilled volume of the drug was decreased."( Ocular bioavailability and systemic loss of topically applied ophthalmic drugs.
Francoeur, M; Patton, TF, 1978
)
0.47
"The bioavailability of topically applied pilocarpine nitrate was studied as a function of instilled volume."( Pharmacokinetic evidence for improved ophthalmic drug delivery by reduction of instilled volume.
Patton, TF, 1977
)
0.52
" By selective variation in experimental conditions, the influence of tear turnover, instilled solution drainage, and nonproductive absorption on ocular drug bioavailability was separately studied and quantitated."( Quantitative precorneal disposition of topically applied pilocarpine nitrate in rabbit eyes.
Patton, TF; Robinson, JR, 1976
)
0.5
" The transcorneal pilocarpine flux is slower than the data appear to indicate, and previous overestimates of the apparent absorption rate constant are due to parallel elimination processes occurring at the absorption site."( Mechanistic studies on transcorneal permeation of pilocarpine.
Robinson, JR; Sieg, JW, 1976
)
0.84
"The bioavailability of topically applied ocular drugs is very poor, due largely to drug loss through drainage and tear turnover."( Influence of topical anesthesia on tear dynamics and ocular drug bioavailability in albino rabbits.
Patton, TF; Robinson, JR, 1975
)
0.25
"The flow properties and viscosity of the vehicle into which drugs are incorporated can be determining factors in the bioavailability of topically applied ophthalmic drugs."( Ocular evaluation of polyvinyl alcohol vehicle in rabbits.
Patton, TF; Robinson, JR, 1975
)
0.25
" It is suggested that the new compounds are prodrug forms of pilocarpine which greatly enhance the corneal bioavailability of the parent compound."( New water-soluble pilocarpine derivatives with enhanced and sustained muscarinic activity.
Bodor, N; Drewniak-Deyrup, M; Druzgala, P; Kaminski, JJ; Smith, S; Winwood, D, 1992
)
0.86
"New alkyl and aralkyl pilocarpic acid diesters, prodrugs of pilocarpine, were synthesized with the aim of improving the bioavailability of pilocarpine by increasing its corneal permeability."( Determination of physicochemical properties, stability in aqueous solutions and serum hydrolysis of pilocarpic acid diesters.
Järvinen, T; Naumanen, H; Peura, P; Suhonen, P; Urtti, A, 1991
)
0.52
" The effect of the polymer solution on the bioavailability of pilocarpine is subsequently assessed by measuring the relative miotic response intensities produced by a 1% solution of the drug."( Evaluation of mucoadhesive polymers in ocular drug delivery. I. Viscous solutions.
Davies, NM; Farr, SJ; Hadgraft, J; Kellaway, IW, 1991
)
0.52
"The bioavailability of drugs from conventional ophthalmic formulations is low."( Sustained release ophthalmic formulations of pilocarpine.
Deshpande, SG; Shirolkar, S, 1989
)
0.54
" These findings indicate that in a comparison of total doses delivered pilocarpine has an approximately eight-fold greater bioavailability from NODS than from a conventional eyedrop formulation."( Relative bioavailability of pilocarpine from a novel ophthalmic delivery system and conventional eyedrop formulations.
Kelly, JA; Molyneux, PD; Smith, SA; Smith, SE, 1989
)
0.8
" The microcapsule suspension showed prolongation of miosis and an improved bioavailability when compared with a standard eye dosage form."( The in vivo evaluation of poly(lactic acid) microcapsules of pilocarpine hydrochloride.
Jalsenjak, I; Pepeljnjak, S; Vidmar, V,
)
0.37
"Various alkyl and aralkyl esters of pilocarpic acid were synthesized and evaluated as prodrug forms for pilocarpine with the purpose of improving the ocular bioavailability of pilocarpine through increased corneal membrane permeability."( Pilocarpine prodrugs I. Synthesis, physicochemical properties and kinetics of lactonization of pilocarpic acid esters.
Bundgaard, H; Falch, E; Larsen, C; Mikkelson, TJ, 1986
)
1.93
" In-vivo miosis vs time experiments on albino rabbits, showed that all inserts increased significantly the bioavailability of pilocarpine, with respect to a standard solution of pilocarpine nitrate."( Vehicle effects in ophthalmic bioavailability: an evaluation of polymeric inserts containing pilocarpine.
Chetoni, P; Chiellini, E; Galli, G; Giannaccini, B; Saettone, MF, 1984
)
0.69
"The bioavailability of topically applied pilocarpine is poor due to various loss mechanisms that serve to lessen delivery of the drug to the aqueous humor."( Quantitative evaluation of topically applied pilocarpine in the precorneal area.
Himmelstein, KJ; Thombre, AG, 1984
)
0.79
" The effect of the coadministered SBE4-beta-CD on the miotic response of pilocarpine solutions was also compared to that of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) which has recently been suggested to increase ocular bioavailability of pilocarpine in rabbits."( The effect of a modified beta-cyclodextrin, SBE4-beta-CD, on the aqueous stability and ocular absorption of pilocarpine.
Järvinen, K; Järvinen, T; Stella, VJ; Thompson, DO, 1994
)
0.73
" To evaluate the ability of hydroxypropyl-beta-cyclodextrins to improve ophthalmic drug bioavailability following topical administration, the miotic effect of topical solutions of pilocarpine was studied in New Zealand White rabbits."( Beta-cyclodextrins enhance bioavailability of pilocarpine.
Crosson, CE; Freedman, KA; Klein, JW, 1993
)
0.74
" A better understanding of the mechanisms involved in transcorneal permeation could lead to improvements in drug dosage forms or the development of drug delivery devices which enhance the ocular bioavailability of drugs."( Theoretical corneal permeation model for ionizable drugs.
Cheng, YL; Friedrich, SW; Saville, BA, 1993
)
0.29
"A new formulation (HYA) based on timolol hyaluronate and pilocarpine hyaluronate salts has been shown to improve the bioavailability of the drugs and to extend the duration of their action."( Pharmacological evaluation of a new timolol/pilocarpine formulation.
Bucolo, C; Mangiafico, S; Spadaro, A, 1998
)
0.81
" This conclusion was based upon their ability to provide a substantial prolongation of drug action and an improvement in the ocular bioavailability of pilocarpine compared to conventional eye drops and previously utilized PF127 formulations of PHCL."( Evaluation of pluronic F127-based sustained-release ocular delivery systems for pilocarpine using the albino rabbit eye model.
Blanchard, J; Desai, SD, 1998
)
0.73
"A new formulation based on pilocarpine hyaluronate salt has been shown to improve the bioavailability of the drug and to extend the duration of activity."( Pharmacological profile of a new topical pilocarpine formulation.
Bucolo, C; Mangiafico, P, 1999
)
0.87
" Although the bioavailability of the drug is pH dependent, emulsions at higher pH cannot be considered for clinical use because of pilocarpine degradation which occurs with a similar rate as in aqueous solutions."( In vivo evaluation of submicron emulsions with pilocarpine: the effect of pH and chemical form of the drug.
Janicki, S; Mackiewicz, J; Sznitowska, M; Zurowska-Pryczkowska, K,
)
0.59
"This work investigates pilocarpine trapped in a matrix diffusion-controlled drug delivery system using hydrophilic inserts of Poly(2-hydroxyethyl methacrylate) (pHEMA) to ensure an increased bioavailability of pilocarpine and prolong the length of time in which the medication remains in the eyes of the test subjects."( Poly(2-hydroxyethyl methacrylate) film as a drug delivery system for pilocarpine.
Cheng, CC; Guu, JA; Hsiue, GH, 2001
)
0.86
" There was a two-fold increase in ocular bioavailability of pilocarpine due to the therapy with micron emulsion."( [Ocular pharmacokinetics of pilocarpine micron emulsion in rabbits].
Chen, Z; Song, J; Xie, L; Xu, Y; Zhang, J, 1999
)
0.84
"Our study results demonstrated significantly increase in ocular bioavailability of pilocarpine due to the therapy with micron emulsion."( [Ocular pharmacokinetics of pilocarpine micron emulsion in rabbits].
Chen, Z; Song, J; Xie, L; Xu, Y; Zhang, J, 1999
)
0.82
"To determine the amount of pupillary constriction to four different concentrations of pilocarpine in normal human subjects and to determine if pupillary constriction correlates with bioavailability of the instilled concentrations."( Pupillary response to four concentrations of pilocarpine in normal subjects: application to testing for Adie tonic pupil.
Brubaker, RF; Hodge, DO; Leavitt, JA; Wayman, LL, 2002
)
0.8
" It is suggested that ocular bioavailability of pilocarpine nitrate could be improved by the addition of HPbetaCD."( Influence of hydroxypropyl beta-cyclodextrin on the corneal permeation of pilocarpine.
Aktaş, Y; Hincal, AA; Irkeç, M; Orhan, M; Unlü, N, 2003
)
0.81
"The results suggest that 1% pilocarpine liposome improves the bioavailability and prolong the duration of its action."( [Action of miosis of 1% pilocarpine liposome in rabbits].
Yao, K; Zhang, HC, 2003
)
0.92
" Liposome formulation can significantly increase the bioavailability of pilocarpine in ocular aqueous."( [Determination of three formulations of pilocarpine in rabbit ocular aqueous by RP-HPLC].
Chen, B; Wang, XJ; Yao, TW; Zeng, S; Zhang, HC, 2004
)
0.82
"5% pilocarpine with sodium hyaluronate significantly increases ocular bioavailability of pilocarpine."( [Ocular pharmacokinetics of 0.5% pilocarpine with sodium hyaluronate in rabbits].
Chen, ZJ; Lü, XF; Pang, GR; Song, JZ; Xu, Y; Zhang, JJ, 2004
)
1.23
"Multidrug resistance proteins (MRPs; symbol ABCC) are membrane glycoproteins that mediate the ATP-dependent export of a wide range of substrates from cells and thereby affect the bioavailability and disposition of many drugs."( Expression of the multidrug transporter MRP2 in the blood-brain barrier after pilocarpine-induced seizures in rats.
Gastens, AM; Hoffmann, K; Löscher, W; Volk, HA, 2006
)
0.56
" Therefore, CS-PN/SE could enhance the duration of action and ocular bioavailability by improving the precorneal residence and ocular absorption significantly."( [Chitosan-coated ophthalmic submicro emulsion for pilocarpine nitrate].
He, HL; Wei, J; Zheng, CL; Zhu, JB, 2011
)
0.62
" Intracameral administration of pilocarpine using GN was found to be more effective than other methods such as instillation of eye drop and injection of free drug or PN containing drug in improving ocular bioavailability and extending the pharmacological responses (i."( A gelatin-g-poly(N-isopropylacrylamide) biodegradable in situ gelling delivery system for the intracameral administration of pilocarpine.
Hsieh, AC; Lai, JY, 2012
)
0.87
" Various studies were performed to improve the bioavailability and prolong the residence time of drugs in ocular drug delivery."( Preparation and characterization of polymeric and lipid nanoparticles of pilocarpine HCl for ocular application.
Lütfi, G; Müzeyyen, D,
)
0.36
"The aim of this study was to improve the stability and bioavailability of pilocarpine in order to maintain an adequate concentration of the pilocarpine at the site of action for prolonged period of time."( Developing the potential ophthalmic applications of pilocarpine entrapped into polyvinylpyrrolidone-poly(acrylic acid) nanogel dispersions prepared by γ radiation.
Abd El-Rehim, HA; Hamed, AA; Hegazy, el-SA; Klingner, A; Swilem, AE, 2013
)
0.87
" hM4Di has no effect in the absence of its selective, normally inactive and orally bioavailable agonist clozapine-N-oxide (CNO)."( Chemical-genetic attenuation of focal neocortical seizures.
Kätzel, D; Kullmann, DM; Nicholson, E; Schorge, S; Walker, MC, 2014
)
0.4
" These data shown that NMD-Lipo has an anticonvulsant activity significantly superior to free NMD, suggesting that the liposomes promoted a drug controlled release by improving its bioavailability and consequently increasing its pharmacological activity."( Acute toxicity and anticonvulsant activity of liposomes containing nimodipine on pilocarpine-induced seizures in mice.
Cavalcanti, IM; Freitas, RM; Moreno, LC; Rolim, HM; Santos-Magalhães, NS; Satyal, P, 2015
)
0.64
", ip) indicate that the liver is the primary site of biotransformation of the compound, suggesting that both 22a and its metabolite(s) are active, compensating probably low bioavailability of the parent molecule."( Design, physico-chemical properties and biological evaluation of some new N-[(phenoxy)alkyl]- and N-{2-[2-(phenoxy)ethoxy]ethyl}aminoalkanols as anticonvulsant agents.
Bednarski, M; Gunia-Krzyżak, A; Marona, H; Nitek, W; Pękala, E; Powroźnik, B; Słoczyńska, K; Walczak, M; Waszkielewicz, AM; Żesławska, E, 2016
)
0.43
" The pharmacokinetics (PK) and bioavailability depend not only on active compound and excipients but also on physicochemical properties of the ocular drug formulation."( General Pharmacokinetic Model for Topically Administered Ocular Drug Dosage Forms.
Deng, F; Kidron, H; Ranta, VP; Urtti, A, 2016
)
0.43
"To improve ocular bioavailability and extend pharmacological response, this study aims to investigate the role of alkyl chain length of monothiol-terminated alkyl carboxylic acids in the synthesis, characterization, and application of gelatin-g-poly(N-isopropylacrylamide) (GN) biodegradable in situ gelling carriers for antiglaucoma drug delivery."( The role of alkyl chain length of monothiol-terminated alkyl carboxylic acid in the synthesis, characterization, and application of gelatin-g-poly(N-isopropylacrylamide) carriers for antiglaucoma drug delivery.
Lai, JY; Luo, LJ, 2017
)
0.46
"Considering that glaucoma is a chronic disease that requires long-term medical therapy to preserve vision in patients, it is highly desirable to augment pharmacological bioavailability and govern release profile by tuning the properties of drug delivery carriers."( The role of alkyl chain length of monothiol-terminated alkyl carboxylic acid in the synthesis, characterization, and application of gelatin-g-poly(N-isopropylacrylamide) carriers for antiglaucoma drug delivery.
Lai, JY; Luo, LJ, 2017
)
0.46
" The aim of efficient ophthalmic drug delivery strategy is to attain the longer precorneal resident time and good bioavailability of drugs."( Effect of cellulose nanocrystals on the performance of drug loaded in situ gelling thermo-responsive ophthalmic formulations.
Bhattacharyya, A; Chattoapadhyay, A; Chattopadhyay, D; Das, B; Das, S; Ghosh, SK; Mishra, R; Orasugh, JT; Roy, I; Saha, NR; Sarkar, G, 2019
)
0.51
"The purpose of this paper was to investigate the potential of liquid crystalline (LC) gels for ophthalmic delivery, so as to enhance the bioavailability of pilocarpine nitrate (PN)."( A Novel Phytantriol-Based Lyotropic Liquid Crystalline Gel for Efficient Ophthalmic Delivery of Pilocarpine Nitrate.
Cao, J; Chu, X; Gui, S; Huang, J; Li, Z; Liu, L; Tian, C; Wang, X; Xia, M; Zhang, Y, 2019
)
0.93
"Extending the delivery of drugs into the eyes while reducing systemic bioavailability is of utmost importance in the management of chronic ocular diseases."( Pharmacokinetics and Tissue Distribution of Pilocarpine After Application to Eyelid Skin of Rats.
Sagesaka, A; See, GL; Sugibayashi, K; Todo, H; Wierzba, K, 2019
)
0.78
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51
"The present study was focused on investigating niosomal gels loaded with cholinergic drug; pilocarpine HCl, for prolonged precorneal residence time and improved bioavailability for glaucoma treatment."( Formulation and investigation of pilocarpine hydrochloride niosomal gels for the treatment of glaucoma: intraocular pressure measurement in white albino rabbits.
Jain, N; Verma, A, 2020
)
1.06

Dosage Studied

This report presents a mathematical model which has been developed to describe the intraocular disposition of pilocarpine following topical dosing in rabbits. Dose-response relationships of pilOCarpine and timolol to lower intraocular pressure were demonstrated with this model. Analysis of the dose-response curves indicated that tropicamide showed approximately the same potency as atropine for pilocARPine.

ExcerptRelevanceReference
"Changes in tear film pH were observed during the 1st hr after instillation of pilocarpine in various dosage forms to the rabbit eye."( Effect of topically applied pilocarpine on tear film pH.
Birss, S; Keller, N; Longwell, A; Moore, D, 1976
)
0.78
" Furthermore, the enhanced toxicity of pilocarpine caused by bamipine in a defined dosage range is antagonized by biperiden in a dose related manner."( [Central and peripheral interactions of the antiparkinson agent biperiden and the antihistaminic bamipin on the rat excited by pilocarpine].
Hofmann, HP; Kreiskott, H, 1978
)
0.73
" Atropine (5 x 10(-6) M) causes a 17-fold shift to the right on the dose-response curve to carbamylcholine."( Potassium release from the rat submaxillary gland in vitro. II. Induction by parasympathomimetic secretagogues.
Martinez, JR; Quissell, DO, 1976
)
0.26
" Analysis of dose-response curves shows that for pepsin secretion the Vmax values were raised by this procedure."( The secretion of pepsin.
Kondo, T; Magee, DF, 1977
)
0.26
" While pilocarpine retained some residual hypotensive effect 12 hours after application, twice-daily dosage with the solutions tested gave inadequate control for clinical usefulness."( Intraocular pressure control with twice-daily pilocarpine in two vehicle solutions.
Pollack, IP; Quigley, HA, 1977
)
0.97
",blinking, and the dosing system emulsifying efficiency."( Vehicle effects on ocular drug bioavailability III: Shear-facilitated pilocarpine release from ointments.
Robinson, JR; Sieg, JW, 1979
)
0.49
" Plastic viscosity parameters correlated to miosis durations in the rabbit following ophthalmic dosing of 50 microliters."( Inlfuence of high-viscosity vehicles on miotic effect of pilocarpine.
DeSantis, LM; Roehrs, RE; Schoenwald, RD; Ward, RL, 1978
)
0.5
" Both blocking agents exert their effects on H--S following dose-response curves which are similar, whatever the drug used to evoke head-shaking."( Blockade of both pilocarpine and amphetamine-induced head-shaking with dopamine receptor antagonists.
Dem, B; Holmgren, B; Urbá-Holmgren, R, 1978
)
0.6
" In the dose-response study pilocarpine was given 1 h prior to the hexobarbital threshold determination."( The interaction between pilocarpine and hexobarbital in male rats.
Wahlström, G, 1976
)
0.86
" The relationship between fraction absorbed and instilled volume was not direct, but appropriate adjustment of instilled volume and concentration should permit substantial dosage reductions without sacrifice of drug concentration in the eye."( Pharmacokinetic evidence for improved ophthalmic drug delivery by reduction of instilled volume.
Patton, TF, 1977
)
0.26
" Incremental doses of amphetamine and pilocarpine correspondingly suppressed PhAD parameters in a dose-response fashion."( Pharmacological suppression of photically evoked after-discharges in rats: incremental dose, hippocampal EEG and behavioral activity correlates.
Bigler, ED; Fleming, DE, 1976
)
0.53
" A narrow bell-shaped dose-response relationship was found."( ACTH: a structure-activity study on pilocarpine-induced epilepsy.
Croiset, G; De Wied, D, 1992
)
0.56
" sweat rate dose-response curves were obtained from each subject using iontophoresis."( Cholinergic sensitivity of the eccrine sweat gland in trained and untrained men.
Buono, MJ; Connolly, KP; White, CS, 1992
)
0.28
" Further studies are required to determine the dose-response relationship, latency and progression of the observed changes."( A pilot study of a method of estimating the number of functional eccrine sweat glands in irradiated human skin.
Dische, S; Morris, WJ; Mott, G, 1992
)
0.28
" A carbachol aerosol dose-response curve was carried out at this time and compared with a control carbachol dose-response curve by calculating the dose of carbachol required to increase RL by 400% (PD400)."( Systemic pilocarpine increases deposition of and decreases responsiveness to inhaled carbachol in sheep.
Forteza, R; Garcia, L; Kim, CS; Wanner, A, 1992
)
0.7
" Whereas castration failed to shift either dose-response curve, ovariectomy mitigated the gender differences in pilocarpine and clonidine analgesia."( Roles of gender and gonadectomy in pilocarpine and clonidine analgesia in rats.
Bodnar, RJ; Kiefel, JM, 1992
)
0.77
" For timolol, nasolacrimal occlusion collapsed the dose-response curve and extended the duration of action."( Therapeutic index of pilocarpine, carbachol, and timolol with nasolacrimal occlusion.
Fuqua, M; Nardin, GF; Sharir, M; Zimmerman, TJ, 1992
)
0.6
" Identically appearing placebo solution with the same dosing schedule and duration was used for the control subjects."( Effects of pilocarpine on salivary flow in patients with Sjögren's syndrome.
Rhodus, NL; Schuh, MJ, 1991
)
0.67
"2 mg/kg) of pilocarpine, a muscarinic agonist, showed a significant improvement of both types of memory deficit with bell shaped dose-response curves."( Differential effects of physostigmine and pilocarpine on the spatial memory deficits produced by two septo-hippocampal deafferentations in rats.
Maeda, N; Matsuoka, N; Ohkubo, Y; Yamaguchi, I, 1991
)
0.92
" The data obtained in the cytogenetic analysis of both dose-response and time-response studies showed a significant induction of C-mitotic effects in the mouse bone marrow."( The effects of pilocarpine nitrate upon the mitotic index of mouse bone marrow cells.
Hegde, MJ; Prabhu, MP, 1991
)
0.63
"01-1 mg/kg) increased the number of penile erections with bell-shaped dose-response curves."( Septohippocampal cholinergic pathway and penile erections induced by dopaminergic and cholinergic stimulants.
Maeda, N; Matsuoka, N; Yamaguchi, I, 1990
)
0.28
" To optimize the therapy, sustained release ophthalmic dosage forms are warranted."( Sustained release ophthalmic formulations of pilocarpine.
Deshpande, SG; Shirolkar, S, 1989
)
0.54
" Dose-response relationships of pilocarpine and timolol to lower intraocular pressure were demonstrated with this model."( Microvascular access to the uveal tract in the rabbit eye for ocular pharmacologic studies.
Chiou, FY; Chiou, GC; Li, BH; Ruiz-Razura, A, 1989
)
0.56
" Dosage comparisons of drug responses were obtained by interpolation and yielded the equivalence of one eyedrop to 67 +/- 11 micrograms pilocarpine from the NODS formulation."( Relative bioavailability of pilocarpine from a novel ophthalmic delivery system and conventional eyedrop formulations.
Kelly, JA; Molyneux, PD; Smith, SA; Smith, SE, 1989
)
0.77
" Denervation caused a shift to the left of the 86Rb efflux dose-response curve to carbachol and phenylephrine (3."( Effect of parasympathetic denervation on K+ release by rat parotid slices.
Adham, N; Templeton, D, 1987
)
0.27
" We established dose-response curves by fluorometric measurement of Ca2+ mobilization in cell suspensions of whole chick embryos stage 23/24."( The muscarinic receptor of chick embryo cells: correlation between ligand binding and calcium mobilization.
Drews, U; Oettling, G; Schmidt, H, 1985
)
0.27
" In the presence of atropine (10(-5) M), the dose-response curve for ACh was shifted to the right."( Voltage-independent catecholamine release mediated by the activation of muscarinic receptors in guinea-pig adrenal glands.
Nakazato, Y; Ohga, A; Oleshansky, M; Tomita, U; Yamada, Y, 1988
)
0.27
" The results show a lowering of the dose-response curve obtained with apomorphine and pilocarpine, as well as a shift to the right in the curve obtained with physostigmine."( Does REM sleep deprivation induce subsensitivity of presynaptic dopamine or postsynaptic acetylcholine receptors in the rat brain?
Braz, S; Neumann, BG; Silva-Filho, AR; Troncone, LR; Tufik, S, 1987
)
0.5
" Dose-response studies show that intravenously administered pilocarpine and intra-arterial acetylcholine stimulate secretion of retinol by the lacrimal gland."( Retinol secretion by the lacrimal gland.
Foley, KM; Rismondo, V; Ubels, JL, 1986
)
0.51
" The microcapsule suspension showed prolongation of miosis and an improved bioavailability when compared with a standard eye dosage form."( The in vivo evaluation of poly(lactic acid) microcapsules of pilocarpine hydrochloride.
Jalsenjak, I; Pepeljnjak, S; Vidmar, V,
)
0.37
" Dose-response curves for pilocarpine and oxotremorine effects are not appreciably affected either by pretreatment with methylatropine (1."( Microwave facilitation of methylatropine antagonism of central cholinomimetic drug effects.
Fujimoto, JM; Ishii, TK; Lange, DG; Quock, RM, 1986
)
0.57
" Applications range from ocular inserts to transdermal patches to oral dosage forms."( Membrane systems: practical applications.
Smith, KL, 1985
)
0.27
" However, the dose-response curve for pilocarpine was steeper than that for apomorphine."( Apomorphine-induced and pilocarpine-induced hypothermia in mice: drug interactions and changes in drug sensitivity after caudate nucleus lesions.
Glick, SD; Marsanico, RG, 1974
)
0.83
" Supersensitivity was observed, after daily oral dosing with hyoscine, in the increased salivation of mice in response to pilocarpine injected at least 66 h after withdrawing hyoscine."( Supersensitivity of salivation in response to pilocarpine after withdrawal of chronically administered hyoscine in the mouse.
Parkes, MW; Parks, JC, 1972
)
0.72
" It is concluded that in clinical dosage mianserin is devoid of effects upon muscarinic receptors, alpha 1 adrenoceptors and noradrenaline uptake in the pupil."( Failure of mianserin to affect autonomic function in the pupils of depressed patients.
Checkley, S; Delgado, I; Shur, E, 1983
)
0.27
" Neither time delay nor this constant was affected by the dose or the dosage form."( Prolonged pulse-entry of pilocarpine with a soluble drug insert.
Juslin, M; Kujari, H; Salminen, L; Urtti, A, 1983
)
0.57
" Under nonlethal conditions of dosage and exposure time, all compounds blocked carbachol-induced paralysis, indicating a possible action at schistosome cholinergic sites."( Schistosoma mansoni: species-selective response to N-chloroethyl-acetylcholine derivatives.
Ahmed, AE; Hillman, GR; Willcockson, WS, 1983
)
0.27
" Any attempt to develop rational age-related dosage modifications for ophthalmic drugs must include a consideration of functional and developmental differences as well as size effects."( Age-related differences in ophthalmic drug disposition I. Effect of size on the intraocular tissue distribution of pilocarpine in albino rabbits.
Miller, SC; Patton, TF,
)
0.34
"This report presents a mathematical model which has been developed to describe the intraocular disposition of pilocarpine following topical dosing in rabbits."( A physiologically based pharmacokinetic model for the intraocular distribution of pilocarpine in rabbits.
Himmelstein, KJ; Miller, SC; Patton, TF, 1981
)
0.7
"Cornea, aqueous humor, and iris-ciliary body levels of pilocarpine and its metabolite pilocarpic acid were determined in mixed-breed rabbits following topical dosing with 25 microliters of 1 X 10(-2) M pilocarpine."( Corneal metabolism of pilocarpine in pigmented rabbits.
Hui, HW; Lee, VH; Robinson, JR, 1980
)
0.82
" Although the 20-microL drop represents a substantial dosage reduction, the miotic response was essentially equivalent to that obtained with the 50-microL drop."( Topically applied pilocarpine. Human pupillary response as a function of drop size.
File, RR; Patton, TF, 1980
)
0.59
" The dose-response curves for SNI-2011 were approximately parallel to curves for pilocarpine but the potency of SNI-2011 was about 25-fold lower than that of pilocarpine."( Sialogogic activities of SNI-2011 compared with those of pilocarpine and McN-A-343 in rat salivary glands: identification of a potential therapeutic agent for treatment of Sjörgen's syndrome.
Iwabuchi, Y; Masuhara, T, 1994
)
0.76
" There was not a significant scopolamine x pilocarpine interaction, suggesting that pretreatment with scopolamine produced an apparent parallel shift in the pilocarpine dose-response curve."( Repeated scopolamine injections sensitize rats to pilocarpine-induced vacuous jaw movements and enhance striatal muscarinic receptor binding.
Baskin, PP; Gianutsos, G; Salamone, JD, 1994
)
0.8
"We tested the hypothesis that a single systemic injection of 380 mg/kg of the muscarinic agonist pilocarpine would produce more diffuse and severe seizure-induced brain damage than a single injection of lithium (3 mEq/kg) followed 4 h later by < 1/10 the dosage of pilocarpine."( Concordance of quantitative damage within the diencephalon and telencephalon following systemic pilocarpine (380 mg/kg) or lithium (3 mEq/kg)/pilocarpine (30 mg/kg) induced seizures.
Bureau, YR; Peredery, O; Persinger, MA, 1994
)
0.72
"05% dipivefrin every 12 hours might be an adequate dosage for maximal effect."( Nasolacrimal occlusion improves the therapeutic index of antiglaucoma medications.
Sharir, M; Zimmerman, TJ, 1994
)
0.29
" A better understanding of the mechanisms involved in transcorneal permeation could lead to improvements in drug dosage forms or the development of drug delivery devices which enhance the ocular bioavailability of drugs."( Theoretical corneal permeation model for ionizable drugs.
Cheng, YL; Friedrich, SW; Saville, BA, 1993
)
0.29
" Because optimal development of P dosage forms for humans requires that its pharmacokinetics and pharmacodynamics be defined, this intravenous study of its disposition and associated salivary responses was performed."( A pharmacokinetic and pharmacodynamic study of intravenous pilocarpine in humans.
Kramer, PA; Schulman, P; Tanzer, JM; Willard, AK, 1995
)
0.53
" Repeated doses of PGF2 alpha-TS or PGF2 alpha-IE did not significantly affect the accommodative response to pilocarpine, while pilocarpine did not alter the approximately 10 mmHg ipsilateral IOP fall induced by repeated dosing of PGF2 alpha-TS or PGF2 alpha-IE."( PGF2 alpha/pilocarpine interactions on IOP and accommodation in monkeys.
Kaufman, PL; Millar, JC, 1995
)
0.89
") induced penile erection in rats, with bell-shaped dose-response curves."( Brain somatostatin depletion by cysteamine attenuates the penile erection induced by serotonergic and dopaminergic, but not by cholinergic, activation in rats.
Maeda, N; Matsuoka, N; Yamaguchi, I; Yamazaki, M, 1996
)
0.29
"We investigated the influence of the streptozocin (STZ)-diabetic state on the dose-response curves for salivary flow and protein content in saliva stimulated by pilocarpine and noradrenaline in mice."( The streptozocin-diabetic state depresses saliva secretion stimulated by pilocarpine and noradrenaline in mice.
Chen, FJ; Kimura, I; Kimura, M; Miyamoto, H, 1996
)
0.72
"05) increase in both parotid and whole saliva output followed all three doses beginning within 1 hour of dosing and lasting over 10 hours."( Pilot study of controlled-release pilocarpine in normal subjects.
Acharya, R; Fox, PC; Gentry, AC; Lockhart, PB; Norton, HJ, 1996
)
0.57
"This investigation was carried out to try the application of pilocarpine hydrochloride (PC) solid dispersion as sustained release dosage form."( [Preparation and evaluation of solid dispersions of pilocarpine hydrochloride for alleviation of xerostomia].
Miyazaki, S; Oda, M; Ohno, K; Sato, M; Takada, M; Watanabe, S; Yagi, N, 1997
)
0.79
" Results showed a significantly improved skin perfusion in the lidocaine-treated group in a dose-response fashion as compared to control animals."( Local anesthetics improve dermal perfusion after burn injury.
Brofeldt, BT; Cassuto, J; Jönsson, A; Nellgård, P; Tarnow, P,
)
0.13
" Granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) act outwith the haemopoeitic system and can reduce mucositis, but the best schedule, dosage and method of administration is not known or which is the best growth factor to prevent this side-effect."( Treatment-induced mucositis: an old problem with new remedies.
Symonds, RP, 1998
)
0.3
" The process of determining dose-response relationships is simplified since an entire dose-response curve can be constructed from a distinct set of cells."( Flow injection microscopy for the study of intracellular calcium mobilization by muscarinic agonists.
Connors, WL; Ruzicka, J, 1999
)
0.3
"To study any interaction between pilocarpine and latanoprost when administered together, and to determine the optimal timing of dosage to maximize reduction of intraocular pressure (IOP)."( Interaction of pilocarpine with latanoprost in patients with glaucoma and ocular hypertension.
Crosson, CE; Hebert, RL; Kent, AR; Thomas, TJ; Vroman, DT, 1999
)
0.94
" There were no significant differences between dosage schedules in the magnitude of the additional reduction in IOP."( Interaction of pilocarpine with latanoprost in patients with glaucoma and ocular hypertension.
Crosson, CE; Hebert, RL; Kent, AR; Thomas, TJ; Vroman, DT, 1999
)
0.66
" The brains of rats that had received this small dosage of lithium and pilocarpine exhibited discernable infiltrations of lymphocytes within limbic tracts but no discernable neuronal loss."( Infiltration of lymphocytes in the limbic brain following stimulation of subclinical cellular immunity and low dosages of lithium and a cholinergic agent.
Cook, LL; Persinger, MA, 1999
)
0.54
"25% drops in twice daily dosage and does not result in any significant ocular and systemic adverse effects."( A prospective, long-term, randomized study of the efficacy and safety of the drug combination pilocarpine 1% with clonidine 0.06% or clonidine 0.125% versus timolol 0.25%.
Agarwal, H; Rajashekhar, YL; Sihota, R; Venkatesh, P, 2002
)
0.53
" In contrast, in human neocortical preparations obtained from epilepsy surgery, in approximately 20% of the slices spontaneous epileptiform activity appeared with this bicuculline dosage without SDs."( Differential sensitivity to induction of spreading depression by partial disinhibition in chronically epileptic human and rat as compared to native rat neocortical tissue.
Hagemann, G; Koch, UR; Köhling, R; Redecker, C; Speckmann, EJ; Straub, H, 2003
)
0.32
"In all age groups, the dosage of DZP that stopped the seizures at 5 min was not effective in terminating seizures at 60 min."( Diazepam terminates brief but not prolonged seizures in young, naïve rats.
Goodkin, HP; Holmes, GL; Liu, X, 2003
)
0.32
" In chlorpyrifos-treated animals, pilocarpine dose-response curves were shifted significantly to the right, demonstrating decreased responsiveness of neuronal M2 receptors."( Mechanisms of organophosphate insecticide-induced airway hyperreactivity.
Beckles, RA; Fryer, AD; Howard, AS; Jett, DA; Lein, PJ; Yost, BL, 2004
)
0.6
" The case is unique in that it is the first reported ingestion of oral pilocarpine tablets and the first dosing error reported for this indication."( Pilocarpine toxicity and the treatment of xerostomia.
Greenberg, MI; Hendrickson, RG; Morocco, AP, 2004
)
2
" The present study, therefore, suggests that the reduction of mGluR2/3 immunopositive product in the SLM of CA1 is a consequence of neuronal loss in either the entorhinal cortex or CA1 area of the hippocampus, and at the dosage range from 12."( Metabotropic glutamate receptor 2/3 in the hippocampus of patients with mesial temporal lobe epilepsy, and of rats and mice after pilocarpine-induced status epilepticus.
Burgunder, JM; Chen, PM; Chia, SC; Gao, H; Lee, WL; Ling, EA; Probst, A; Sim, MK; Tang, FR; Yeo, TS,
)
0.34
"75-75 mg/kg, sc) shifted pilocarpine dose-response curves significantly to the right, indicating loss of neuronal M2 receptor function."( Organophosphorus insecticides induce airway hyperreactivity by decreasing neuronal M2 muscarinic receptor function independent of acetylcholinesterase inhibition.
Fryer, AD; Lein, PJ, 2005
)
0.63
" Initially, dose-response experiments were performed with intrahippocampal perfusions of GBR-12909 and citalopram, respectively, selective dopamine and serotonin re-uptake blockers."( Anticonvulsant action of GBR-12909 and citalopram against acute experimentally induced limbic seizures.
Clinckers, R; Ebinger, G; Meurs, A; Michotte, Y; Smolders, I, 2004
)
0.32
" The conclusions generally discusses the usability of equations and their correct interperetation in modelling dissolution of active ingrediens from dosage forms."( [Weibull equation and dissolution kinetics].
Zatloukal, Z, 2004
)
0.32
" Mortality was not affected by the dosage of paraldehyde."( Outcome of status epilepticus in immature rats varies according to the paraldehyde treatment.
Kubová, H; Mares, P; Redkozubova, O; Rejchrtová, J, 2005
)
0.33
"4 mg/5 microl pilocarpine intracerebroventricularly, to obtain the dose-response relationship for behavioural seizures."( Arginine vasopressin does not contribute to seizures induced by intracerebroventricularly-injected pilocarpine.
Gulec, G; Isbil-Buyukcoskun, N, 2005
)
0.91
"Patients using ophthalmic drops are faced with frequent dosing schedules and difficult drop instillation."( Characterization of pilocarpine-loaded chitosan/Carbopol nanoparticles.
Kao, HJ; Lin, HR; Lo, YL; Yu, SP, 2006
)
0.66
" The antagonistic effect of darifenacin against the dose-response curves for pilocarpine appeared to be insurmountable."( In vivo demonstration of M3 muscarinic receptor subtype selectivity of darifenacin in mice.
Maruyama, S; Oki, T; Takagi, Y; Uchida, S; Yamada, S, 2006
)
0.56
" Analysis of the dose-response curves indicated that tropicamide showed approximately the same potency as atropine for suppression of pilocarpine-induced jaw movements but was more potent than atropine on the suppression of pimozide-induced jaw movements."( The muscarinic receptor antagonist tropicamide suppresses tremulous jaw movements in a rodent model of parkinsonian tremor: possible role of M4 receptors.
Betz, AJ; Burgos, M; McLaughlin, PJ; Salamone, JD; Weber, SM, 2007
)
0.54
" In order to ensure the occurrence of status epilepticus (SE) and decrease mortality, individual dosing of pilocarpine was performed by ramping up the dose until onset of SE."( Behavioral alterations in the pilocarpine model of temporal lobe epilepsy in mice.
Gröticke, I; Hoffmann, K; Löscher, W, 2007
)
0.84
" In B6JOla and B6NHsd, only a small percentage of mice developed SE independently of whether pilocarpine was administered at high bolus doses or with a ramping up dosing protocol, but mortality was high."( Differences in sensitivity to the convulsant pilocarpine in substrains and sublines of C57BL/6 mice.
Gröticke, I; Hoffmann, K; Löscher, W; Müller, CJ; Schughart, K, 2009
)
0.83
" After withdrawal of the EP1 receptor antagonist, a low dose of the P-glycoprotein substrate phenobarbital resulted in an anticonvulsant effect in this pretreated group, whereas the same dosage of phenobarbital did not exert a significant effect in the respective control group."( Targeting prostaglandin E2 EP1 receptors prevents seizure-associated P-glycoprotein up-regulation.
Bauer, B; Gorter, JA; Hartz, AM; Pekcec, A; Potschka, H; Schlichtiger, J; Soerensen, J; Unkrüer, B; van Vliet, EA, 2009
)
0.35
" For this study, we used the same pilocarpine ramping-up dosing protocol and behavioral test battery than in a previous study in NMRI mice, thus allowing direct comparison between these two mouse strains."( Behavioral and cognitive alterations, spontaneous seizures, and neuropathology developing after a pilocarpine-induced status epilepticus in C57BL/6 mice.
Bankstahl, M; Gröticke, I; Löscher, W; Müller, CJ, 2009
)
0.85
" For prostaglandins, dosing time was suggested in the morning by 18 (36%) ophthalmologists and in the evening by 24 (48%) (p=0."( Ophthalmologist attitudes regarding fixed combination treatment for glaucoma in the European Union.
Kruft, B; Nelson, LA; Stewart, JA; Stewart, WC,
)
0.13
" In the present retrospective study we evaluated the impact of these vendor changes on ketamine dosing to establish anaesthesia, on pilocarpine-induced seizure susceptibility, and on basal extracellular hippocampal noradrenaline, dopamine, serotonin, gamma-amino butyric acid, and glutamate levels of all pilocarpine-treated rats included in our studies."( Intrastrain differences in seizure susceptibility, pharmacological response and basal neurochemistry of Wistar rats.
Aourz, N; Clinckers, R; De Bundel, D; Meurs, A; Michotte, Y; Portelli, J; Smolders, I, 2009
)
0.56
" Based on pharmacokinetic studies with bumetanide, which showed extremely rapid elimination and low brain penetration of this drug in rats, bumetanide was administered systemically with different dosing protocols, including continuous intravenous infusion."( Disease-modifying effects of phenobarbital and the NKCC1 inhibitor bumetanide in the pilocarpine model of temporal lobe epilepsy.
Brandt, C; Heuchert, N; Löscher, W; Nozadze, M; Rattka, M, 2010
)
0.58
" The data will allow developing dosing regimens for evaluation of whether treatment with subconvulsant doses of PTZ during the latent period affects the development of epilepsy."( Enhanced susceptibility to the GABA antagonist pentylenetetrazole during the latent period following a pilocarpine-induced status epilepticus in rats.
Bankstahl, M; Brandt, C; Bröer, S; Löscher, W; Rattka, M,
)
0.35
"The authors conclude that mucoadhesive microparticles formulated into a dry dosage form is a promising system for sustained drug delivery to the eye."( Mucoadhesive microparticles in a rapidly dissolving tablet for sustained drug delivery to the eye.
Choy, YB; Edelhauser, HF; McCarey, BE; Park, JH; Patel, SR; Prausnitz, MR, 2011
)
0.37
" Plasma TRP/LNAAS ratios increased 2- to 3-fold after dosing with ALAC (250 mg/kg/day) for 7 and 14 days, respectively."( Preclinical activity profile of α-lactoalbumin, a whey protein rich in tryptophan, in rodent models of seizures and epilepsy.
Citraro, R; De Fazio, S; De Sarro, G; Mainardi, P; Perucca, E; Raggio, R; Russo, E; Scicchitano, F, 2011
)
0.37
" These findings suggest that dosing of topical medications may need to be increased in eyes with a history of CXL to achieve expected therapeutic effects, and they may have implications for the long-term health of the cornea."( Cross-linking with ultraviolet-a and riboflavin reduces corneal permeability.
Lamy, R; Lee, OT; Schultz, DS; Stewart, JM; Wong, FF, 2011
)
0.37
" We assessed, quantitatively and morphometrically, glial fibrillary acidic protein (GFAP) expression and cell densities in hippocampus in a dose-response manner 2, 4 and 8 weeks after the pilocarpine insult."( Glial activation in a pilocarpine rat model for epileptogenesis: a morphometric and quantitative analysis.
Corona-Morales, AA; Escobar, A; Estrada, FS; Hernández, VS; López-Hernández, E; Solís, H; Zhang, L, 2012
)
0.88
" We used male NMRI mice (28-32 g) and first established the dose-response relationship for pilocarpine (250-400 mg/kg; ip) to induce status epilepticus (SE)."( Rapid epileptogenesis in the mouse pilocarpine model: video-EEG, pharmacokinetic and histopathological characterization.
Kaminski, RM; Kumar, G; Mazzuferi, M; Rospo, C, 2012
)
0.88
" The estimated 24-hour potency (expressed as concentration of dosing solution) was 45."( In vivo pharmacological characterization of TD-4208, a novel lung-selective inhaled muscarinic antagonist with sustained bronchoprotective effect in experimental animal models.
Hegde, SS; Jaw-Tsai, S; Ji, Y; Martin, WJ; McNamara, A; Obedencio, GP; Pulido-Rios, MT, 2013
)
0.39
" Luteolin did not exhibit any consistent anti- or pro-convulsant actions after single dosing in the 6 Hz (0."( Anticonvulsant screening of luteolin in four mouse seizure models.
Borges, K; Shaikh, MF; Tan, KN, 2013
)
0.39
" To allow efficient xenotransplantation for the purpose of optimizing potential cell-based therapy of human TLE, we have determined the optimal dosing strategy to produce spontaneous recurring seizures in immunodeficient NodScid mice."( Optimization of pilocarpine-mediated seizure induction in immunodeficient NodScid mice.
Ahn, S; Chung, S; Cunningham, M; Iskandar, D; Kim, KS; Kim, Y; Leung, A; Luna, MJ; Savvidis, G, 2015
)
0.76
" Further analysis was performed to assess the dose-response effect on the risk of dry eye according to the cumulative number of different types of glaucoma medications used."( Association between Glaucoma Medication Usage and Dry Eye in Taiwan.
Chen, HY; Kao, CH; Lin, CL; Tsai, YY, 2015
)
0.42
" The animals were randomized into groups and were administered one of the following treatments: saline, PILO, saline+L-α-aminoadipic acid (L-AAA; one dosage tested), PILO+L-AAA, or PILO+L-methionine sulfoximine (three dosages tested)."( A sub-threshold dose of pilocarpine increases glutamine synthetase in reactive astrocytes and enhances the progression of amygdaloid-kindling epilepsy in rats.
Bai, XY; Chen, XM; Deng, DP; Li, SC; Liu, YX; Pan, XH; Sun, HL; Wang, CH; Wang, CY; Zhang, XL; Zhu, W, 2016
)
0.74
"The pharmacokinetics of the sublingual fentanyl orally disintegrating tablet appear to be negatively affected by the presence of salivary gland hypofunction, although the moistening of the oral cavity before dosing results in a pharmacokinetic profile similar to that seen with the giving of pilocarpine hydrochloride."( The Influence of Low Salivary Flow Rates on the Absorption of a Sublingual Fentanyl Citrate Formulation for Breakthrough Cancer Pain.
Buchanan, A; Davies, A; Mundin, G; Vriens, J; Waghorn, M; Webber, K, 2016
)
0.61
" Pilocarpine was administered by a ramp-up dosing protocol that allows determining interindividual differences in susceptibility to the convulsant."( The pilocarpine model of temporal lobe epilepsy: Marked intrastrain differences in female Sprague-Dawley rats and the effect of estrous cycle.
Bankstahl, M; Brandt, C; Klee, R; Löscher, W; Töllner, K, 2016
)
1.9
"Pilocarpine hydrochloride is commonly prescribed to patients with dry mouth and eye using a frequent dosing schedule."( The Sustained Effects on Tear Volume of Pilocarpine Hydrochloride in Gelatin by Hydrogel Administered by An Implant-mediated Drug Delivery System.
Cha, S; Kho, HS; Kim, HK; Park, YS, 2017
)
2.17
" Also demonstrated is reduction of the traditional iontophoretic dosage for sweat stimulation (<5."( Prolonged and localized sweat stimulation by iontophoretic delivery of the slowly-metabolized cholinergic agent carbachol.
Heikenfeld, J; Kasting, G; Li, SK; Simmers, P, 2018
)
0.48
"Clinical factors contributing to benzodiazepine failure in treating status epilepticus (SE) include suboptimal dosing and seizure duration."( Status epilepticus: Role for etiology in determining response to benzodiazepines.
Chester, SJ; Goodkin, HP; Hawk, KM; Joshi, S; Rajasekaran, K, 2018
)
0.48
"Development of biodegradable thermogels as intracameral injectable carriers for ocular delivery of antiglaucoma medications can provide a better treatment modality with low dosing frequency than eye drop formulations."( Effect of deacetylation degree on controlled pilocarpine release from injectable chitosan-g-poly(N-isopropylacrylamide) carriers.
Chen, HC; Huang, CC; Lai, JY; Luo, LJ; Matsusaki, M, 2018
)
0.74
"The goal was to synthesize novel preactivated chitosan conjugates and to design adhesive dosage forms comprising sialagogue pilocarpine."( Buccal adhesive chitosan conjugate comprising pilocarpine for xerostomia.
Laffleur, F; Röttges, S, 2019
)
0.98
"The novelty of this promising polymeric carrier lies in the synthesis procedure leading to a pronounced mucoadhesive, mucoprotecting and controlled release encouraging dosage form in the management of xerostomia."( Buccal adhesive chitosan conjugate comprising pilocarpine for xerostomia.
Laffleur, F; Röttges, S, 2019
)
0.77
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
antiglaucoma drugAny drug which can be used to prevent or alleviate glaucoma, a disease in which the optic nerve is damaged, resulting in progressive, irreversible loss of vision. It is often, though not always, associated with increased pressure of the fluid in the eye.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
pilocarpine
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (44)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, MAJOR APURINIC/APYRIMIDINIC ENDONUCLEASEHomo sapiens (human)Potency8.91250.003245.467312,589.2998AID2517
thioredoxin reductaseRattus norvegicus (Norway rat)Potency0.82720.100020.879379.4328AID488773; AID588453
GLS proteinHomo sapiens (human)Potency3.98110.35487.935539.8107AID624146
regulator of G-protein signaling 4Homo sapiens (human)Potency12.59390.531815.435837.6858AID504845
cytochrome P450 family 3 subfamily A polypeptide 4Homo sapiens (human)Potency0.34670.01237.983543.2770AID1645841
arylsulfatase AHomo sapiens (human)Potency2.39341.069113.955137.9330AID720538
euchromatic histone-lysine N-methyltransferase 2Homo sapiens (human)Potency15.46750.035520.977089.1251AID504332
cytochrome P450 2C19 precursorHomo sapiens (human)Potency7.94330.00255.840031.6228AID899
cytochrome P450 2C9 precursorHomo sapiens (human)Potency15.84890.00636.904339.8107AID883
chromobox protein homolog 1Homo sapiens (human)Potency25.11890.006026.168889.1251AID488953
peptidyl-prolyl cis-trans isomerase NIMA-interacting 1Homo sapiens (human)Potency8.49210.425612.059128.1838AID504536
cytochrome P450 3A4 isoform 1Homo sapiens (human)Potency15.84890.031610.279239.8107AID884; AID885
lamin isoform A-delta10Homo sapiens (human)Potency0.28180.891312.067628.1838AID1487
Gamma-aminobutyric acid receptor subunit piRattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-1Rattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit deltaRattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-5Rattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-3Rattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-1Rattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-2Rattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-4Rattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-3Rattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-6Rattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
Histamine H2 receptorCavia porcellus (domestic guinea pig)Potency15.84890.00638.235039.8107AID883
Spike glycoproteinSevere acute respiratory syndrome-related coronavirusPotency3.16230.009610.525035.4813AID1479145
Gamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-3Rattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
GABA theta subunitRattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit epsilonRattus norvegicus (Norway rat)Potency15.84891.000012.224831.6228AID885
ATP-dependent phosphofructokinaseTrypanosoma brucei brucei TREU927Potency0.67460.060110.745337.9330AID485368
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Muscarinic acetylcholine receptor M2Homo sapiens (human)Ki12.02260.00000.690210.0000AID322941
Muscarinic acetylcholine receptor M1Rattus norvegicus (Norway rat)IC50 (µMol)3.02670.00052.773925.1700AID104017; AID141540; AID141554
Muscarinic acetylcholine receptor M1Rattus norvegicus (Norway rat)Ki3.67000.00010.579710.0000AID142348
Muscarinic acetylcholine receptor M3Rattus norvegicus (Norway rat)IC50 (µMol)3.84000.00052.891925.1700AID104017; AID141540
Muscarinic acetylcholine receptor M3Rattus norvegicus (Norway rat)Ki3.67000.00011.48339.1400AID142348
Muscarinic acetylcholine receptor M4Rattus norvegicus (Norway rat)IC50 (µMol)3.84000.00052.747825.1700AID104017; AID141540
Muscarinic acetylcholine receptor M4Rattus norvegicus (Norway rat)Ki3.67000.00010.68688.2600AID142348
Muscarinic acetylcholine receptor M5Rattus norvegicus (Norway rat)IC50 (µMol)3.84000.00052.780225.1700AID104017; AID141540
Muscarinic acetylcholine receptor M5Rattus norvegicus (Norway rat)Ki3.67000.00010.66618.2600AID142348
Muscarinic acetylcholine receptor M5Homo sapiens (human)Ki10.23290.00000.72926.9183AID322942
Muscarinic acetylcholine receptor M2Rattus norvegicus (Norway rat)IC50 (µMol)3.84000.00053.314249.5000AID104017; AID141540
Muscarinic acetylcholine receptor M2Rattus norvegicus (Norway rat)Ki3.67000.00010.58908.2600AID142348
Muscarinic acetylcholine receptor M1Homo sapiens (human)Ki7.27510.00000.59729.1201AID1199354; AID322940
Cytochrome P450 2A6Homo sapiens (human)Ki3.00000.00561.52717.5000AID1209284
Muscarinic acetylcholine receptor DM1Drosophila melanogaster (fruit fly)Ki2.89000.00051.42495.2000AID1090601; AID1090602
Cytochrome P450 2A13Homo sapiens (human)Ki1.40000.04002.71005.6000AID1209281
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Muscarinic acetylcholine receptor M2Homo sapiens (human)EC50 (µMol)63.00000.00000.737810.0000AID142417
Muscarinic acetylcholine receptor M1Homo sapiens (human)EC50 (µMol)3.21380.00161.304310.0000AID1193905; AID1199331; AID142284
Muscarinic acetylcholine receptor M1Homo sapiens (human)Kd2.69150.00090.98292.6915AID1199333; AID1199354
Cytochrome P450 2A6Homo sapiens (human)Kd3.60000.68003.19506.2000AID1209277
Muscarinic acetylcholine receptor M1Mus musculus (house mouse)EC50 (µMol)6.90000.27004.29006.9000AID141319
Cytochrome P450 2A13Homo sapiens (human)Kd3.00000.43003.18008.2000AID1209286
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Muscarinic acetylcholine receptor M1Rattus norvegicus (Norway rat)K app1.62400.00000.98246.2000AID142097; AID142098; AID142209; AID142210; AID142211; AID142212
Muscarinic acetylcholine receptor M3Rattus norvegicus (Norway rat)K app1.62400.00000.98246.2000AID142097; AID142098; AID142209; AID142210; AID142211; AID142212
Muscarinic acetylcholine receptor M4Rattus norvegicus (Norway rat)K app1.62400.00000.98246.2000AID142097; AID142098; AID142209; AID142210; AID142211; AID142212
Muscarinic acetylcholine receptor M5Rattus norvegicus (Norway rat)K app1.62400.00000.98246.2000AID142097; AID142098; AID142209; AID142210; AID142211; AID142212
Muscarinic acetylcholine receptor M2Rattus norvegicus (Norway rat)K app1.62400.00001.00846.2000AID142097; AID142098; AID142209; AID142210; AID142211; AID142212
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (35)

Processvia Protein(s)Taxonomy
G protein-coupled receptor signaling pathwayMuscarinic acetylcholine receptor M2Homo sapiens (human)
adenylate cyclase-modulating G protein-coupled receptor signaling pathwayMuscarinic acetylcholine receptor M2Homo sapiens (human)
phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathwayMuscarinic acetylcholine receptor M2Homo sapiens (human)
G protein-coupled acetylcholine receptor signaling pathwayMuscarinic acetylcholine receptor M2Homo sapiens (human)
nervous system developmentMuscarinic acetylcholine receptor M2Homo sapiens (human)
regulation of heart contractionMuscarinic acetylcholine receptor M2Homo sapiens (human)
response to virusMuscarinic acetylcholine receptor M2Homo sapiens (human)
G protein-coupled serotonin receptor signaling pathwayMuscarinic acetylcholine receptor M2Homo sapiens (human)
presynaptic modulation of chemical synaptic transmissionMuscarinic acetylcholine receptor M2Homo sapiens (human)
regulation of smooth muscle contractionMuscarinic acetylcholine receptor M2Homo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathwayMuscarinic acetylcholine receptor M2Homo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerMuscarinic acetylcholine receptor M2Homo sapiens (human)
chemical synaptic transmissionMuscarinic acetylcholine receptor M2Homo sapiens (human)
gastric acid secretionMuscarinic acetylcholine receptor M5Homo sapiens (human)
G protein-coupled acetylcholine receptor signaling pathwayMuscarinic acetylcholine receptor M5Homo sapiens (human)
dopamine transportMuscarinic acetylcholine receptor M5Homo sapiens (human)
transmission of nerve impulseMuscarinic acetylcholine receptor M5Homo sapiens (human)
regulation of phosphatidylinositol dephosphorylationMuscarinic acetylcholine receptor M5Homo sapiens (human)
G protein-coupled serotonin receptor signaling pathwayMuscarinic acetylcholine receptor M5Homo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerMuscarinic acetylcholine receptor M5Homo sapiens (human)
chemical synaptic transmissionMuscarinic acetylcholine receptor M5Homo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathwayMuscarinic acetylcholine receptor M5Homo sapiens (human)
positive regulation of monoatomic ion transportMuscarinic acetylcholine receptor M1Homo sapiens (human)
signal transductionMuscarinic acetylcholine receptor M1Homo sapiens (human)
G protein-coupled receptor signaling pathwayMuscarinic acetylcholine receptor M1Homo sapiens (human)
protein kinase C-activating G protein-coupled receptor signaling pathwayMuscarinic acetylcholine receptor M1Homo sapiens (human)
phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathwayMuscarinic acetylcholine receptor M1Homo sapiens (human)
G protein-coupled acetylcholine receptor signaling pathwayMuscarinic acetylcholine receptor M1Homo sapiens (human)
neuromuscular synaptic transmissionMuscarinic acetylcholine receptor M1Homo sapiens (human)
nervous system developmentMuscarinic acetylcholine receptor M1Homo sapiens (human)
regulation of locomotionMuscarinic acetylcholine receptor M1Homo sapiens (human)
saliva secretionMuscarinic acetylcholine receptor M1Homo sapiens (human)
cognitionMuscarinic acetylcholine receptor M1Homo sapiens (human)
regulation of postsynaptic membrane potentialMuscarinic acetylcholine receptor M1Homo sapiens (human)
regulation of glial cell proliferationMuscarinic acetylcholine receptor M1Homo sapiens (human)
positive regulation of intracellular protein transportMuscarinic acetylcholine receptor M1Homo sapiens (human)
G protein-coupled serotonin receptor signaling pathwayMuscarinic acetylcholine receptor M1Homo sapiens (human)
postsynaptic modulation of chemical synaptic transmissionMuscarinic acetylcholine receptor M1Homo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerMuscarinic acetylcholine receptor M1Homo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathwayMuscarinic acetylcholine receptor M1Homo sapiens (human)
chemical synaptic transmissionMuscarinic acetylcholine receptor M1Homo sapiens (human)
xenobiotic metabolic processCytochrome P450 2A6Homo sapiens (human)
steroid metabolic processCytochrome P450 2A6Homo sapiens (human)
coumarin metabolic processCytochrome P450 2A6Homo sapiens (human)
xenobiotic catabolic processCytochrome P450 2A6Homo sapiens (human)
coumarin catabolic processCytochrome P450 2A6Homo sapiens (human)
epoxygenase P450 pathwayCytochrome P450 2A6Homo sapiens (human)
coumarin metabolic processCytochrome P450 2A13Homo sapiens (human)
aflatoxin metabolic processCytochrome P450 2A13Homo sapiens (human)
xenobiotic metabolic processCytochrome P450 2A13Homo sapiens (human)
epoxygenase P450 pathwayCytochrome P450 2A13Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (13)

Processvia Protein(s)Taxonomy
G protein-coupled acetylcholine receptor activityMuscarinic acetylcholine receptor M2Homo sapiens (human)
arrestin family protein bindingMuscarinic acetylcholine receptor M2Homo sapiens (human)
G protein-coupled serotonin receptor activityMuscarinic acetylcholine receptor M2Homo sapiens (human)
phosphatidylinositol phospholipase C activityMuscarinic acetylcholine receptor M5Homo sapiens (human)
protein bindingMuscarinic acetylcholine receptor M5Homo sapiens (human)
G protein-coupled acetylcholine receptor activityMuscarinic acetylcholine receptor M5Homo sapiens (human)
G protein-coupled serotonin receptor activityMuscarinic acetylcholine receptor M5Homo sapiens (human)
phosphatidylinositol phospholipase C activityMuscarinic acetylcholine receptor M1Homo sapiens (human)
protein bindingMuscarinic acetylcholine receptor M1Homo sapiens (human)
G protein-coupled acetylcholine receptor activityMuscarinic acetylcholine receptor M1Homo sapiens (human)
G protein-coupled serotonin receptor activityMuscarinic acetylcholine receptor M1Homo sapiens (human)
iron ion bindingCytochrome P450 2A6Homo sapiens (human)
coumarin 7-hydroxylase activityCytochrome P450 2A6Homo sapiens (human)
enzyme bindingCytochrome P450 2A6Homo sapiens (human)
heme bindingCytochrome P450 2A6Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygenCytochrome P450 2A6Homo sapiens (human)
arachidonic acid epoxygenase activityCytochrome P450 2A6Homo sapiens (human)
monooxygenase activityCytochrome P450 2A13Homo sapiens (human)
iron ion bindingCytochrome P450 2A13Homo sapiens (human)
coumarin 7-hydroxylase activityCytochrome P450 2A13Homo sapiens (human)
heme bindingCytochrome P450 2A13Homo sapiens (human)
aromatase activityCytochrome P450 2A13Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygenCytochrome P450 2A13Homo sapiens (human)
arachidonic acid epoxygenase activityCytochrome P450 2A13Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (20)

Processvia Protein(s)Taxonomy
plasma membraneMuscarinic acetylcholine receptor M2Homo sapiens (human)
membraneMuscarinic acetylcholine receptor M2Homo sapiens (human)
clathrin-coated endocytic vesicle membraneMuscarinic acetylcholine receptor M2Homo sapiens (human)
asymmetric synapseMuscarinic acetylcholine receptor M2Homo sapiens (human)
symmetric synapseMuscarinic acetylcholine receptor M2Homo sapiens (human)
presynaptic membraneMuscarinic acetylcholine receptor M2Homo sapiens (human)
neuronal cell bodyMuscarinic acetylcholine receptor M2Homo sapiens (human)
axon terminusMuscarinic acetylcholine receptor M2Homo sapiens (human)
postsynaptic membraneMuscarinic acetylcholine receptor M2Homo sapiens (human)
glutamatergic synapseMuscarinic acetylcholine receptor M2Homo sapiens (human)
cholinergic synapseMuscarinic acetylcholine receptor M2Homo sapiens (human)
plasma membraneMuscarinic acetylcholine receptor M2Homo sapiens (human)
synapseMuscarinic acetylcholine receptor M2Homo sapiens (human)
dendriteMuscarinic acetylcholine receptor M2Homo sapiens (human)
plasma membraneMuscarinic acetylcholine receptor M5Homo sapiens (human)
postsynaptic membraneMuscarinic acetylcholine receptor M5Homo sapiens (human)
dendriteMuscarinic acetylcholine receptor M5Homo sapiens (human)
plasma membraneMuscarinic acetylcholine receptor M5Homo sapiens (human)
synapseMuscarinic acetylcholine receptor M5Homo sapiens (human)
plasma membraneMuscarinic acetylcholine receptor M1Homo sapiens (human)
membraneMuscarinic acetylcholine receptor M1Homo sapiens (human)
presynaptic membraneMuscarinic acetylcholine receptor M1Homo sapiens (human)
axon terminusMuscarinic acetylcholine receptor M1Homo sapiens (human)
Schaffer collateral - CA1 synapseMuscarinic acetylcholine receptor M1Homo sapiens (human)
postsynaptic density membraneMuscarinic acetylcholine receptor M1Homo sapiens (human)
glutamatergic synapseMuscarinic acetylcholine receptor M1Homo sapiens (human)
cholinergic synapseMuscarinic acetylcholine receptor M1Homo sapiens (human)
synapseMuscarinic acetylcholine receptor M1Homo sapiens (human)
dendriteMuscarinic acetylcholine receptor M1Homo sapiens (human)
plasma membraneMuscarinic acetylcholine receptor M1Homo sapiens (human)
endoplasmic reticulum membraneCytochrome P450 2A6Homo sapiens (human)
cytoplasmic microtubuleCytochrome P450 2A6Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 2A6Homo sapiens (human)
cytoplasmCytochrome P450 2A6Homo sapiens (human)
plasma membraneGamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)
virion membraneSpike glycoproteinSevere acute respiratory syndrome-related coronavirus
plasma membraneGamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)
plasma membraneGamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)
endoplasmic reticulum membraneCytochrome P450 2A13Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 2A13Homo sapiens (human)
cytoplasmCytochrome P450 2A13Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (170)

Assay IDTitleYearJournalArticle
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID142098In vitro displacement of [3H]OXO-M from muscarinic acetylcholine receptor in rat cortical homogenates1990Journal of medicinal chemistry, Apr, Volume: 33, Issue:4
Novel quinuclidine-based ligands for the muscarinic cholinergic receptor.
AID141540Ability to displace [3H]cis--2-methyl-5-((dimethylamino)methyl)-1,3-di oxolane from muscarinic acetylcholine receptor in rat cortical tissue.1992Journal of medicinal chemistry, Jan, Volume: 35, Issue:1
Muscarinic activity of the thiolactone, lactam, lactol, and thiolactol analogues of pilocarpine and a hypothetical model for the binding of agonists to the m1 receptor.
AID114232Salivation after subcutaneous administration in mice1998Journal of medicinal chemistry, Oct-22, Volume: 41, Issue:22
Muscarinic agonists with antipsychotic-like activity: structure-activity relationships of 1,2,5-thiadiazole analogues with functional dopamine antagonist activity.
AID1199347Partial agonist activity at human muscarinic M1 acetylcholine receptor expressed in CHO cells assessed as increase in IP1 accumulation at 100 uM incubated for 30 mins in presence of 100 ng/ml Gi protein inhibitor PTX by FRET based HTRF assay2015Journal of medicinal chemistry, Jan-22, Volume: 58, Issue:2
Rational design of partial agonists for the muscarinic m1 acetylcholine receptor.
AID1090593Toxicity to Musca domestica (house fly) assessed as mortality at 75 ug/fly measured after 0.5 hr2007Journal of agricultural and food chemistry, Mar-21, Volume: 55, Issue:6
Insect muscarinic acetylcholine receptor: pharmacological and toxicological profiles of antagonists and agonists.
AID625279Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID233564The ratio of Kapp([3H]-NMS) / Kapp([3H]-OXO-M) was determined1990Journal of medicinal chemistry, Apr, Volume: 33, Issue:4
Novel quinuclidine-based ligands for the muscarinic cholinergic receptor.
AID625284Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID142369The selectivity ratio of Kapp of NMS/OXO -M1990Journal of medicinal chemistry, Oct, Volume: 33, Issue:10
Synthesis and biological activity of 1,2,4-oxadiazole derivatives: highly potent and efficacious agonists for cortical muscarinic receptors.
AID141319Tested against Muscarinic acetylcholine receptor M1 expressed in A9 L cell line1997Journal of medicinal chemistry, Apr-11, Volume: 40, Issue:8
Synthesis and biological characterization of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine derivatives as selective m1 agonists.
AID588216FDA HLAED, serum glutamic oxaloacetic transaminase (SGOT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID141436Maximum stimulation at Muscarinic acetylcholine receptor M1 expressed in A9 L cells1997Journal of medicinal chemistry, Apr-11, Volume: 40, Issue:8
Synthesis and biological characterization of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine derivatives as selective m1 agonists.
AID588218FDA HLAED, lactate dehydrogenase (LDH) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID142417Stimulation of cAMP in CHO cells expressing human m2 receptor1998Bioorganic & medicinal chemistry letters, Oct-20, Volume: 8, Issue:20
Identification of side chains on 1,2,5-thiadiazole-azacycles optimal for muscarinic m1 receptor activation.
AID1209284Mixed inhibition of CYP2A6 (unknown origin)2012Drug metabolism and disposition: the biological fate of chemicals, Sep, Volume: 40, Issue:9
Evaluation of inhibition selectivity for human cytochrome P450 2A enzymes.
AID1090601Displacement of [3H]QNB from Drosophila melanogaster mAChR by scintillation counting2007Journal of agricultural and food chemistry, Mar-21, Volume: 55, Issue:6
Insect muscarinic acetylcholine receptor: pharmacological and toxicological profiles of antagonists and agonists.
AID230727Ratio of the Ki (NMS) value to that of Ki (Oxo-M).1995Journal of medicinal chemistry, Apr-28, Volume: 38, Issue:9
In vitro muscarinic activity of spiromuscarones and related analogs.
AID588213Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in non-rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID178179Inhibition of conditioned avoidance response in rat following s.c. administration.1998Journal of medicinal chemistry, Oct-22, Volume: 41, Issue:22
Muscarinic agonists with antipsychotic-like activity: structure-activity relationships of 1,2,5-thiadiazole analogues with functional dopamine antagonist activity.
AID142349Binding affinity against muscarinic acetylcholine receptor from rat brain crude membrane, using [3H]OXO-M (oxotremorine) as the radioligand.1995Journal of medicinal chemistry, Apr-28, Volume: 38, Issue:9
In vitro muscarinic activity of spiromuscarones and related analogs.
AID1193910Agonist activity at human m4 muscarinic acetylcholine receptor expressed in HEK293 cells by calcium mobilization assay at 10 microM by FLIPR assay relative to 100 nM acetylcholine response2015Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7
Synthesis and biological evaluation of isoxazoline derivatives as potent M₁ muscarinic acetylcholine receptor agonists.
AID197273Maximum stimulation of phosphatidyl inositol in rat hippocampal tissue, activity is expressed as percent of carbachol response1995Journal of medicinal chemistry, Apr-28, Volume: 38, Issue:9
In vitro muscarinic activity of spiromuscarones and related analogs.
AID1090596Toxicity to Musca domestica (house fly) assessed as mortality at 25 ug/fly measured after 1.5 hr2007Journal of agricultural and food chemistry, Mar-21, Volume: 55, Issue:6
Insect muscarinic acetylcholine receptor: pharmacological and toxicological profiles of antagonists and agonists.
AID625290Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID588214FDA HLAED, liver enzyme composite activity2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID225548Binding affinity against muscarinic receptor in rat brain membranes using oxotremorine-M as ligand1998Bioorganic & medicinal chemistry letters, Oct-20, Volume: 8, Issue:20
Identification of side chains on 1,2,5-thiadiazole-azacycles optimal for muscarinic m1 receptor activation.
AID588212Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID588217FDA HLAED, serum glutamic pyruvic transaminase (SGPT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID1209285Ratio of Ki for CYP2A6 (unknown origin) to Ki for CYP2A13 (unknown origin)2012Drug metabolism and disposition: the biological fate of chemicals, Sep, Volume: 40, Issue:9
Evaluation of inhibition selectivity for human cytochrome P450 2A enzymes.
AID104017Inhibition of [3H]-(R)-QNB binding to muscarinic receptors of rat brain membranes.1993Journal of medicinal chemistry, Apr-02, Volume: 36, Issue:7
Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists.
AID142097In vitro for its ability to displace [3H]NMS from muscarinic acetylcholine receptor in rat cortical homogenates1990Journal of medicinal chemistry, Apr, Volume: 33, Issue:4
Novel quinuclidine-based ligands for the muscarinic cholinergic receptor.
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID588215FDA HLAED, alkaline phosphatase increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID141554Ability to displace [3H]pirenzepine (pir) from muscarinic acetylcholine receptor M1 in rat cortical tissue.1992Journal of medicinal chemistry, Jan, Volume: 35, Issue:1
Muscarinic activity of the thiolactone, lactam, lactol, and thiolactol analogues of pilocarpine and a hypothetical model for the binding of agonists to the m1 receptor.
AID142501In vitro inhibition of [3H]Oxo-Mas binding to M1 and M4 receptors in rat brain homogenate.1998Journal of medicinal chemistry, Oct-22, Volume: 41, Issue:22
Muscarinic agonists with antipsychotic-like activity: structure-activity relationships of 1,2,5-thiadiazole analogues with functional dopamine antagonist activity.
AID1199348Partial agonist activity at human muscarinic M1 acetylcholine receptor expressed in CHO cells assessed as increase in IP1 accumulation at 100 uM incubated for 30 mins in presence of 1 uM Gq protein inhibitor UBO-QIC by FRET based HTRF assay2015Journal of medicinal chemistry, Jan-22, Volume: 58, Issue:2
Rational design of partial agonists for the muscarinic m1 acetylcholine receptor.
AID1090597Toxicity to Musca domestica (house fly) assessed as mortality at 25 ug/fly measured after 1 hr2007Journal of agricultural and food chemistry, Mar-21, Volume: 55, Issue:6
Insect muscarinic acetylcholine receptor: pharmacological and toxicological profiles of antagonists and agonists.
AID196226Tested for agonist activity through assays of phosphoinositide (PI) metabolism in slices from rat cerebral cortex1997Journal of medicinal chemistry, Apr-11, Volume: 40, Issue:8
Synthesis and biological characterization of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine derivatives as selective m1 agonists.
AID1193908Agonist activity at human m2 muscarinic acetylcholine receptor expressed in HEK293 cells by calcium mobilization assay at 10 microM by FLIPR assay relative to 100 nM acetylcholine response2015Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7
Synthesis and biological evaluation of isoxazoline derivatives as potent M₁ muscarinic acetylcholine receptor agonists.
AID625289Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID142081Inhibition of [3H]OXO-M binding against muscarinic acetylcholine receptor in rat brain membranes1991Journal of medicinal chemistry, Nov, Volume: 34, Issue:11
Synthesis, molecular modeling studies, and muscarinic receptor activity of azaprophen analogues.
AID193265Central postsynaptic muscarinic activity was measured relative to muscurine (100%)1992Journal of medicinal chemistry, Jan, Volume: 35, Issue:1
Muscarinic activity of the thiolactone, lactam, lactol, and thiolactol analogues of pilocarpine and a hypothetical model for the binding of agonists to the m1 receptor.
AID1199331Partial agonist activity at human muscarinic M1 acetylcholine receptor expressed in CHO cells assessed as increase in IP1 accumulation incubated for 30 mins by FRET based HTRF assay2015Journal of medicinal chemistry, Jan-22, Volume: 58, Issue:2
Rational design of partial agonists for the muscarinic m1 acetylcholine receptor.
AID142078The compound was tested for inhibition of [3H]NMS binding against muscarinic acetylcholine receptor in rat brain1991Journal of medicinal chemistry, Nov, Volume: 34, Issue:11
Synthesis, molecular modeling studies, and muscarinic receptor activity of azaprophen analogues.
AID140934Central presynaptic activity as effect on electrically evoked acetylcholine release from rat hippocampal slices (M2 model)1992Journal of medicinal chemistry, Jan, Volume: 35, Issue:1
Muscarinic activity of the thiolactone, lactam, lactol, and thiolactol analogues of pilocarpine and a hypothetical model for the binding of agonists to the m1 receptor.
AID1090590Toxicity to Musca domestica (house fly) assessed as mortality at 75 ug/fly measured after 2.5 hr2007Journal of agricultural and food chemistry, Mar-21, Volume: 55, Issue:6
Insect muscarinic acetylcholine receptor: pharmacological and toxicological profiles of antagonists and agonists.
AID1090592Toxicity to Musca domestica (house fly) assessed as mortality at 75 ug/fly measured after 1 hr2007Journal of agricultural and food chemistry, Mar-21, Volume: 55, Issue:6
Insect muscarinic acetylcholine receptor: pharmacological and toxicological profiles of antagonists and agonists.
AID633991Antifungal activity against Saccharomyces cerevisiae ATCC 24657 assessed as growth inhibition after 24 to 48 hrs by agar plate bioassay2012European journal of medicinal chemistry, Jan, Volume: 47, Issue:1
Antifungal activities of novel non-azole molecules against S. cerevisiae and C. albicans.
AID1090602Displacement of [3H]AF-DX 384 from Drosophila melanogaster mAChR by scintillation counting2007Journal of agricultural and food chemistry, Mar-21, Volume: 55, Issue:6
Insect muscarinic acetylcholine receptor: pharmacological and toxicological profiles of antagonists and agonists.
AID588219FDA HLAED, gamma-glutamyl transferase (GGT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID625286Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID112391Tremor after subcutaneous administration in mice was determined1998Journal of medicinal chemistry, Oct-22, Volume: 41, Issue:22
Muscarinic agonists with antipsychotic-like activity: structure-activity relationships of 1,2,5-thiadiazole analogues with functional dopamine antagonist activity.
AID197332Neuronal postsynaptic muscarinic activity was measured by firing rate of the rat hippocampal CA1 neurons in M1 model1992Journal of medicinal chemistry, Jan, Volume: 35, Issue:1
Muscarinic activity of the thiolactone, lactam, lactol, and thiolactol analogues of pilocarpine and a hypothetical model for the binding of agonists to the m1 receptor.
AID142430Stimulation of cAMP in CHO cells expressing human m2 receptor1998Bioorganic & medicinal chemistry letters, Oct-20, Volume: 8, Issue:20
Identification of side chains on 1,2,5-thiadiazole-azacycles optimal for muscarinic m1 receptor activation.
AID1199354Binding affinity to muscarinic M1 acetylcholine receptor (unknown origin)2015Journal of medicinal chemistry, Jan-22, Volume: 58, Issue:2
Rational design of partial agonists for the muscarinic m1 acetylcholine receptor.
AID169191Conditioned avoidance responding in rat after subcutaneous administration (1 mg/kg); expressed as avoidance response/response failure; 18/211998Journal of medicinal chemistry, Oct-22, Volume: 41, Issue:22
Muscarinic agonists with antipsychotic-like activity: structure-activity relationships of 1,2,5-thiadiazole analogues with functional dopamine antagonist activity.
AID625291Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID386623Inhibition of 4-(4-(dimethylamino)styryl)-N-methylpyridinium uptake at human OCT1 expressed in HEK293 cells at 100 uM by confocal microscopy2008Journal of medicinal chemistry, Oct-09, Volume: 51, Issue:19
Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1.
AID113681Inhibition of apomorphine-induced climbing following s.c. administration in mice.1998Journal of medicinal chemistry, Oct-22, Volume: 41, Issue:22
Muscarinic agonists with antipsychotic-like activity: structure-activity relationships of 1,2,5-thiadiazole analogues with functional dopamine antagonist activity.
AID142348Binding affinity against muscarinic acetylcholine receptor from rat brain crude membrane, using [3H]-NMS (N-Methylscopolamine) as the radioligand.1995Journal of medicinal chemistry, Apr-28, Volume: 38, Issue:9
In vitro muscarinic activity of spiromuscarones and related analogs.
AID1090595Toxicity to Musca domestica (house fly) assessed as mortality at 25 ug/fly measured after 2.5 hr2007Journal of agricultural and food chemistry, Mar-21, Volume: 55, Issue:6
Insect muscarinic acetylcholine receptor: pharmacological and toxicological profiles of antagonists and agonists.
AID226748Potency ratio of EC50 of the CHO cell lines to that of A9L cell lines was calculated.1998Bioorganic & medicinal chemistry letters, Oct-20, Volume: 8, Issue:20
Identification of side chains on 1,2,5-thiadiazole-azacycles optimal for muscarinic m1 receptor activation.
AID322941Binding affinity to human cloned muscarinic M2 receptor expressed in CHO cells2008Bioorganic & medicinal chemistry, Mar-15, Volume: 16, Issue:6
Docking analyses on human muscarinic receptors: unveiling the subtypes peculiarities in agonists binding.
AID141133Tested in vitro for agonistic effect on Muscarinic acetylcholine receptor of guinea pig ileum1989Journal of medicinal chemistry, Jun, Volume: 32, Issue:6
Cyclic carbamate analogues of pilocarpine.
AID322942Binding affinity to human cloned muscarinic M5 receptor expressed in CHO cells2008Bioorganic & medicinal chemistry, Mar-15, Volume: 16, Issue:6
Docking analyses on human muscarinic receptors: unveiling the subtypes peculiarities in agonists binding.
AID189455Ability to stimulate phosphoinositol metabolism was examined in the rat cerebral cortex at 100 uM1993Journal of medicinal chemistry, Apr-02, Volume: 36, Issue:7
Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists.
AID1090594Toxicity to Musca domestica (house fly) assessed as mortality at 25 ug/fly measured after 24 hr2007Journal of agricultural and food chemistry, Mar-21, Volume: 55, Issue:6
Insect muscarinic acetylcholine receptor: pharmacological and toxicological profiles of antagonists and agonists.
AID588220Literature-mined public compounds from Kruhlak et al phospholipidosis modelling dataset2008Toxicology mechanisms and methods, , Volume: 18, Issue:2-3
Development of a phospholipidosis database and predictive quantitative structure-activity relationship (QSAR) models.
AID588211Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in humans2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID142210In vitro binding affinity against muscarinic acetylcholine receptor from rat cortical homogenates using [3H]oxotremorine-M radioligand1990Journal of medicinal chemistry, Oct, Volume: 33, Issue:10
Synthesis and biological activity of 1,2,4-oxadiazole derivatives: highly potent and efficacious agonists for cortical muscarinic receptors.
AID142300Stimulation of phosphoinositide hydrolysis in A9L cells expressing human m1 receptor1998Bioorganic & medicinal chemistry letters, Oct-20, Volume: 8, Issue:20
Identification of side chains on 1,2,5-thiadiazole-azacycles optimal for muscarinic m1 receptor activation.
AID193266Neuronal postsynaptic muscarinic activity was measured relative to muscurine (100%)1992Journal of medicinal chemistry, Jan, Volume: 35, Issue:1
Muscarinic activity of the thiolactone, lactam, lactol, and thiolactol analogues of pilocarpine and a hypothetical model for the binding of agonists to the m1 receptor.
AID625280Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1090591Toxicity to Musca domestica (house fly) assessed as mortality at 75 ug/fly measured after 1.5 hr2007Journal of agricultural and food chemistry, Mar-21, Volume: 55, Issue:6
Insect muscarinic acetylcholine receptor: pharmacological and toxicological profiles of antagonists and agonists.
AID1193906Agonist activity at human m1 muscarinic acetylcholine receptor expressed in HEK293 cells by calcium mobilization assay at 10 microM by FLIPR assay relative to 100 nM acetylcholine response2015Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7
Synthesis and biological evaluation of isoxazoline derivatives as potent M₁ muscarinic acetylcholine receptor agonists.
AID101732Peripheral postsynaptic muscarinic activity was measured relative to muscarine (100%)1992Journal of medicinal chemistry, Jan, Volume: 35, Issue:1
Muscarinic activity of the thiolactone, lactam, lactol, and thiolactol analogues of pilocarpine and a hypothetical model for the binding of agonists to the m1 receptor.
AID141848Ratio of ability to displace pirenzpine compared to ability to displace CD (non-selective muscarinic agonist).1992Journal of medicinal chemistry, Jan, Volume: 35, Issue:1
Muscarinic activity of the thiolactone, lactam, lactol, and thiolactol analogues of pilocarpine and a hypothetical model for the binding of agonists to the m1 receptor.
AID1199332Partial agonist activity at human muscarinic M1 acetylcholine receptor expressed in CHO cells assessed as increase in IP1 accumulation incubated for 30 mins by FRET based HTRF assay relative to 100 uM acetylcholine2015Journal of medicinal chemistry, Jan-22, Volume: 58, Issue:2
Rational design of partial agonists for the muscarinic m1 acetylcholine receptor.
AID1199333Displacement of [3H]NMS from human muscarinic M1 acetylcholine receptor expressed in CHO cell membranes by radioligand binding assay2015Journal of medicinal chemistry, Jan-22, Volume: 58, Issue:2
Rational design of partial agonists for the muscarinic m1 acetylcholine receptor.
AID141063Agonism of Muscarinic acetylcholine receptor M3 was determined as maximal contraction rate of isolated guinea pig ileum; 30-50%2004Bioorganic & medicinal chemistry letters, Jun-21, Volume: 14, Issue:12
Discovering selective agonists of endothelial target for acetylcholine (ETA) via diversity-guided pharmacophore simplification and simulation.
AID1209286Binding affinity to CYP2A13 (unknown origin) assessed as type 2 interaction as increase in absorbance 431 to 432 nm and decrease in 406 to 412 nm2012Drug metabolism and disposition: the biological fate of chemicals, Sep, Volume: 40, Issue:9
Evaluation of inhibition selectivity for human cytochrome P450 2A enzymes.
AID588209Literature-mined public compounds from Greene et al multi-species hepatotoxicity modelling dataset2010Chemical research in toxicology, Jul-19, Volume: 23, Issue:7
Developing structure-activity relationships for the prediction of hepatotoxicity.
AID625288Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID142488Inhibition of specific [3H](R)-QNB binding to Muscarinic acetylcholine receptor in rat brain membranes1997Journal of medicinal chemistry, Apr-11, Volume: 40, Issue:8
Synthesis and biological characterization of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine derivatives as selective m1 agonists.
AID142079Inhibition of [3H]QNB binding against muscarinic acetylcholine receptor in rat brain.1991Journal of medicinal chemistry, Nov, Volume: 34, Issue:11
Synthesis, molecular modeling studies, and muscarinic receptor activity of azaprophen analogues.
AID625292Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1150250Toxicity in guinea pig ileum assessed as spasmogenic activity at 0.6 ug/ml1976Journal of medicinal chemistry, Jul, Volume: 19, Issue:7
Quaternary pilocarpine derivatives as potential acetylcholine antagonists. 2. Alterations in the lactone and imidazole moieties.
AID142212In vitro binding affinity against cortical muscarinic acetylcholine receptor measured by displacement of [3H]OXO-M.1992Journal of medicinal chemistry, Jan-24, Volume: 35, Issue:2
Synthesis and muscarinic activity of quinuclidinyl- and (1-azanorbornyl)pyrazine derivatives.
AID1209281Competitive inhibition of CYP2A13 (unknown origin)2012Drug metabolism and disposition: the biological fate of chemicals, Sep, Volume: 40, Issue:9
Evaluation of inhibition selectivity for human cytochrome P450 2A enzymes.
AID197176Central postsynaptic muscarinic activity was measured by slow depolarization of the rat cervical ganglion in M1 model1992Journal of medicinal chemistry, Jan, Volume: 35, Issue:1
Muscarinic activity of the thiolactone, lactam, lactol, and thiolactol analogues of pilocarpine and a hypothetical model for the binding of agonists to the m1 receptor.
AID1209279Ratio of Kd for CYP2A6 (unknown origin) to Kd for CYP2A13 assessed as type 2 interaction as increase in absorbance 431 to 432 nm and decrease in 406 to 412 nm2012Drug metabolism and disposition: the biological fate of chemicals, Sep, Volume: 40, Issue:9
Evaluation of inhibition selectivity for human cytochrome P450 2A enzymes.
AID732891Induction of seizures in ddY mouse at 300 mg/kg, sc measured for 45 mins after drug injection2013ACS medicinal chemistry letters, Feb-14, Volume: 4, Issue:2
Discovery of novel N-substituted oxindoles as selective m1 and m4 muscarinic acetylcholine receptors partial agonists.
AID625285Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID142299Stimulation of phosphoinositide hydrolysis in BHK cells expressing human m1 receptor1998Bioorganic & medicinal chemistry letters, Oct-20, Volume: 8, Issue:20
Identification of side chains on 1,2,5-thiadiazole-azacycles optimal for muscarinic m1 receptor activation.
AID1209277Binding affinity to CYP2A6 (unknown origin) assessed as type 2 interaction as increase in absorbance 431 to 432 nm and decrease in 406 to 412 nm2012Drug metabolism and disposition: the biological fate of chemicals, Sep, Volume: 40, Issue:9
Evaluation of inhibition selectivity for human cytochrome P450 2A enzymes.
AID1193905Agonist activity at human m1 muscarinic acetylcholine receptor expressed in HEK293 cells assessed as calcium mobilization by FLIPR assay2015Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7
Synthesis and biological evaluation of isoxazoline derivatives as potent M₁ muscarinic acetylcholine receptor agonists.
AID26763Compound was evaluated for apparent partition coefficient (log P) between octanol and 0.05 M phosphate buffer solution of pH 7.401985Journal of medicinal chemistry, Aug, Volume: 28, Issue:8
Pilocarpic acid esters as novel sequentially labile pilocarpine prodrugs for improved ocular delivery.
AID1193909Agonist activity at human m3 muscarinic acetylcholine receptor expressed in HEK293 cells by calcium mobilization assay at 10 microM by FLIPR assay relative to 100 nM acetylcholine response2015Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7
Synthesis and biological evaluation of isoxazoline derivatives as potent M₁ muscarinic acetylcholine receptor agonists.
AID625281Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625282Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID142209In vitro binding affinity against muscarinic acetylcholine receptor from rat cortical homogenates using [3H]N-methylscopolamine as radioligand1990Journal of medicinal chemistry, Oct, Volume: 33, Issue:10
Synthesis and biological activity of 1,2,4-oxadiazole derivatives: highly potent and efficacious agonists for cortical muscarinic receptors.
AID1090589Toxicity to Musca domestica (house fly) assessed as mortality at 75 ug/fly measured after 24 hr2007Journal of agricultural and food chemistry, Mar-21, Volume: 55, Issue:6
Insect muscarinic acetylcholine receptor: pharmacological and toxicological profiles of antagonists and agonists.
AID588210Human drug-induced liver injury (DILI) modelling dataset from Ekins et al2010Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 38, Issue:12
A predictive ligand-based Bayesian model for human drug-induced liver injury.
AID1090598Toxicity to Musca domestica (house fly) assessed as mortality at 25 ug/fly measured after 0.5 hr2007Journal of agricultural and food chemistry, Mar-21, Volume: 55, Issue:6
Insect muscarinic acetylcholine receptor: pharmacological and toxicological profiles of antagonists and agonists.
AID227718Binding energy by using the equation deltaG obsd = -RT ln KD1984Journal of medicinal chemistry, Dec, Volume: 27, Issue:12
Functional group contributions to drug-receptor interactions.
AID142211In vitro binding affinity against cortical muscarinic acetylcholine receptor measured by displacement of [3H]NMS.1992Journal of medicinal chemistry, Jan-24, Volume: 35, Issue:2
Synthesis and muscarinic activity of quinuclidinyl- and (1-azanorbornyl)pyrazine derivatives.
AID322940Binding affinity to human cloned muscarinic M1 receptor expressed in CHO cells2008Bioorganic & medicinal chemistry, Mar-15, Volume: 16, Issue:6
Docking analyses on human muscarinic receptors: unveiling the subtypes peculiarities in agonists binding.
AID66346Agonism of endothelin A receptor was determined as maximal rate of vascular endothelium-dependent relaxation at the concentration of 10E-5 M/L; - = no activity2004Bioorganic & medicinal chemistry letters, Jun-21, Volume: 14, Issue:12
Discovering selective agonists of endothelial target for acetylcholine (ETA) via diversity-guided pharmacophore simplification and simulation.
AID625287Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID142368Ratio of geometric mean of the affinity constant (Kapp) of NMS/OXO-M1992Journal of medicinal chemistry, Jan-24, Volume: 35, Issue:2
Synthesis and muscarinic activity of quinuclidinyl- and (1-azanorbornyl)pyrazine derivatives.
AID101734Peripheral postsynaptic muscarinic activity by contraction of the guinea pig ileum.1992Journal of medicinal chemistry, Jan, Volume: 35, Issue:1
Muscarinic activity of the thiolactone, lactam, lactol, and thiolactol analogues of pilocarpine and a hypothetical model for the binding of agonists to the m1 receptor.
AID1193911Agonist activity at human m5 muscarinic acetylcholine receptor expressed in HEK293 cells by calcium mobilization assay at 10 microM by FLIPR assay relative to 100 nM acetylcholine response2015Bioorganic & medicinal chemistry letters, Apr-01, Volume: 25, Issue:7
Synthesis and biological evaluation of isoxazoline derivatives as potent M₁ muscarinic acetylcholine receptor agonists.
AID625283Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID142284Stimulation of phosphoinositide hydrolysis in A9L cells expressing human m1 receptor1998Bioorganic & medicinal chemistry letters, Oct-20, Volume: 8, Issue:20
Identification of side chains on 1,2,5-thiadiazole-azacycles optimal for muscarinic m1 receptor activation.
AID1347410qHTS for inhibitors of adenylyl cyclases using a fission yeast platform: a pilot screen against the NCATS LOPAC library2019Cellular signalling, 08, Volume: 60A fission yeast platform for heterologous expression of mammalian adenylyl cyclases and high throughput screening.
AID1347049Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot screen2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347151Optimization of GU AMC qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID588378qHTS for Inhibitors of ATXN expression: Validation
AID1347086qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347058CD47-SIRPalpha protein protein interaction - HTRF assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347057CD47-SIRPalpha protein protein interaction - LANCE assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID504836Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in human glioma: Validation2002The Journal of biological chemistry, Apr-19, Volume: 277, Issue:16
Sustained ER Ca2+ depletion suppresses protein synthesis and induces activation-enhanced cell death in mast cells.
AID588349qHTS for Inhibitors of ATXN expression: Validation of Cytotoxic Assay
AID1347045Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot counterscreen GloSensor control cell line2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID504812Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1347405qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS LOPAC collection2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347050Natriuretic polypeptide receptor (hNpr2) antagonism - Pilot subtype selectivity assay2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID504810Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1347059CD47-SIRPalpha protein protein interaction - Alpha assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347082qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347083qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347108qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347102qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347092qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347101qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347097qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347099qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347407qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Pharmaceutical Collection2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347424RapidFire Mass Spectrometry qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347425Rhodamine-PBP qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347089qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347091qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347100qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347098qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347090qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID1347107qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347094qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347105qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347095qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347093qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347096qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347103qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347106qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347104qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID504749qHTS profiling for inhibitors of Plasmodium falciparum proliferation2011Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043
Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
AID1345189Rat M1 receptor (Acetylcholine receptors (muscarinic))1989The Journal of pharmacology and experimental therapeutics, Feb, Volume: 248, Issue:2
Pharmacological characterization of the M1 muscarinic receptors expressed in murine fibroblast B82 cells.
AID1345465Human M4 receptor (Acetylcholine receptors (muscarinic))1997Molecular pharmacology, Jul, Volume: 52, Issue:1
Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.
AID1345543Human M5 receptor (Acetylcholine receptors (muscarinic))2005The Journal of pharmacology and experimental therapeutics, Oct, Volume: 315, Issue:1
Persistent binding and functional antagonism by xanomeline at the muscarinic M5 receptor.
AID1345286Human M1 receptor (Acetylcholine receptors (muscarinic))1997Molecular pharmacology, Jul, Volume: 52, Issue:1
Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.
AID1345343Human M3 receptor (Acetylcholine receptors (muscarinic))1997Molecular pharmacology, Jul, Volume: 52, Issue:1
Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.
AID1345326Human M2 receptor (Acetylcholine receptors (muscarinic))1997Molecular pharmacology, Jul, Volume: 52, Issue:1
Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (6,905)

TimeframeStudies, This Drug (%)All Drugs %
pre-19902998 (43.42)18.7374
1990's1027 (14.87)18.2507
2000's1209 (17.51)29.6817
2010's1347 (19.51)24.3611
2020's324 (4.69)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 84.12

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index84.12 (24.57)
Research Supply Index8.95 (2.92)
Research Growth Index4.49 (4.65)
Search Engine Demand Index159.21 (26.88)
Search Engine Supply Index2.04 (0.95)

This Compound (84.12)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials340 (4.64%)5.53%
Reviews198 (2.70%)6.00%
Case Studies269 (3.67%)4.05%
Observational5 (0.07%)0.25%
Other6,522 (88.93%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (55)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Investigating the Stability, Variability and Mechanism of Incorporation of Lipid Mediators Into Eccrine Sweat [NCT02935894]14 participants (Actual)Interventional2016-11-28Completed
A Twelve-Week, Double Masked, Parallel Group, Primary-Therapy Pilot Study of the Safety and Efficacy of Travoprost 0.004% Compared to Pilocarpine 1% in Patients With Chronic Angle-Closure Glaucoma [NCT00762645]Phase 430 participants (Actual)Interventional2007-02-28Completed
Multicenter, Randomized, Double-Masked, Placebo-Controlled, Parallel Group Phase 2 Trial Evaluating the Safety and Efficacy of Pilocarpine Ophthalmic Topical Cream BID for the Treatment of Signs and Symptoms of Dry Eye Disease [NCT05119920]Phase 2226 participants (Actual)Interventional2022-01-03Completed
A Phase 1 Combined Single and Multiple Ascending Oral Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP6282 in Healthy Nonelderly and Elderly Male and Female Subjects, Including a Food Effect Cohort and Drug-drug [NCT02420782]Phase 1116 participants (Actual)Interventional2015-05-31Completed
A Multi-Center, Double-Masked, Vehicle-Controlled, Evaluation of the Efficacy and Safety of CSF-1 in the Temporary Correction of Presbyopia (the NEAR-2 Study: Near Eye-vision Acuity Restoration) [NCT04599972]Phase 3304 participants (Actual)Interventional2020-10-26Completed
A Multi-Center, Double-Masked, Vehicle-Controlled, Evaluation of the Efficacy and Safety of CSF-1 in the Temporary Correction of Presbyopia (the NEAR-1 Study: Near Eye-vision Acuity Restoration) [NCT04599933]Phase 3309 participants (Actual)Interventional2020-10-18Completed
In Vivo Morphological Changes of Ciliary Body and Trabecular Meshwork in High Myopia Eyes With Open-angle Glaucoma in Their Accommodation Induced by Pilocarpine [NCT05352854]120 participants (Anticipated)Interventional2022-05-01Not yet recruiting
A Pilot Study to Compare the Efficacy of Pilocarpine Microneedles With Iontophoresis Method for Sweat Induction in Healthy Human Subjects [NCT04732195]50 participants (Actual)Interventional2022-01-20Completed
Observational Study on the Predictive Value of the BAMCOG and Cortisol Levels for the Incidence of Postoperative Delirium/Postoperative Acute Encephalopathy Measured by the MoCA and the DeltaScan in Patients Who Undergo Aortic Valve Replacement Surgery [NCT05209555]50 participants (Actual)Observational2022-01-10Completed
Evaluating Non-Invasive Measurement of Sweat Glucose of Patients With Diabetes - The ENGAGE Study [NCT03460964]2 participants (Actual)Interventional2018-05-01Terminated(stopped due to Could not perform accurate measures due to equipment and sensor issues.)
A Phase 3, Multicenter, Double-Masked, Randomized, Vehicle-Controlled, Parallel-Group Study Evaluating the Safety and Efficacy of AGN-190584 in Participants With Presbyopia [NCT03857542]Phase 3427 participants (Actual)Interventional2019-03-01Completed
Randomized, Double-Masked, Placebo-Controlled, Multicenter, Phase 3 Study of the Safety and Efficacy of Nyxol (Phentolamine Ophthalmic Solution 0.75%) as a Single Agent and With Adjunctive Low-Dose Pilocarpine Hydrochloride Ophthalmic Solution 0.4% in Sub [NCT05646719]Phase 3333 participants (Actual)Interventional2022-12-22Completed
A Single Dose, Two-Treatment, Two-Period, Two Sequence Crossover Bioequivalency Study of 5 mg Pilocarpine Tablets Under Fed Conditions [NCT00601211]28 participants (Actual)Interventional2003-09-30Completed
The Effect of Cataract Extraction on the Contractility of Ciliary Muscle [NCT00624039]15 participants (Actual)Interventional2006-05-31Enrolling by invitation
Dose, Effects and Characteristics of Pilocarpine [NCT00803803]Phase 437 participants (Actual)Interventional1978-08-31Completed
The International Collaborative Exfoliation Syndrome Treatment Study [NCT00804115]277 participants (Actual)Interventional2000-08-31Active, not recruiting
A Phase 1/2, Randomized, Placebo Controlled Crossover Study to Assess the Safety, Pharmacodynamics, and Efficacy of EXP039 Ophthalmic Solution in Participants With Myopia or Hyperopia [NCT04883996]Phase 1/Phase 260 participants (Anticipated)Interventional2020-12-01Enrolling by invitation
Efficacy of Pilocarpine 1% in Pseudophakia Individuals With Presbyopia [NCT05578001]Phase 325 participants (Anticipated)Interventional2022-07-01Active, not recruiting
Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) With Pilocarpine Eye Drops in Subjects With Presbyopia [NCT04675151]Phase 2150 participants (Actual)Interventional2021-02-15Completed
A Phase II/III Study Comparing Acupuncture-like Transcutaneous Electrical Nerve Stimulation (ALTENS) Versus Pilocarpine in Treating Early Radiation-Induced Xerostomia [NCT00656513]Phase 2/Phase 3196 participants (Actual)Interventional2008-09-30Completed
A Phase 3 Study of the Safety and Efficacy of 1% and 2% Pilocarpine Ophthalmic Solutions Administered With the Optejet® Microdose Dispenser for Temporary Improvement of Near Vision in Adults With Presbyopia [NCT04657172]Phase 384 participants (Actual)Interventional2020-12-15Completed
Effects of THVD-201 on Pharmacokinetics and Pharmacodynamics of Tolterodine in Healthy Subjects [NCT01036035]Phase 118 participants (Actual)Interventional2009-09-30Completed
A Single Dose, Two-Period, Two-Treatment, 2-Sequence Crossover Bioequivalency Study of 7.5 mg Pilocarpine Tablets Under Fed Conditions [NCT00618059]28 participants (Actual)Interventional2004-08-31Completed
Laser Peripheral Iridotomy Plus Laser Peripheral Iridoplasty for Primary Angle Closure With Multi-mechanism Based on UBM: A Randomized Controlled Trial [NCT02613013]240 participants (Anticipated)Interventional2015-10-31Recruiting
A Phase 3, Multicenter, Double-Masked, Randomized, Vehicle-Controlled, Parallel-Group Study Evaluating the Safety and Efficacy of BID Dosing of AGN-190584 in Subjects With Presbyopia [NCT04983589]Phase 3230 participants (Actual)Interventional2021-09-02Completed
Pilocarpine for Vaginal Dryness: A Phase III Randomized, Double Blind, Placebo-Controlled Study [NCT00343382]Phase 3201 participants (Actual)Interventional2006-12-31Completed
A Phase 3 Study of the Safety and Efficacy of 2% Pilocarpine Ophthalmic Spray Administered With the Optejet® Microdose Dispenser for Temporary Improvement of Near Vision in Adults With Presbyopia [NCT05114486]Phase 3145 participants (Actual)Interventional2021-11-03Completed
A Single Dose, Two-Treatment, Two-Period, Two Sequence Crossover Bioequivalency Study of 5 mg Pilocarpine Tablets Under Fasting Conditions [NCT00601874]28 participants (Actual)Interventional2003-09-30Completed
A Single Dose, Two-Period, Two-Treatment, 2-Sequence Crossover Bioequivalency Study of 7.5 mg Pilocarpine Tablets Under Fasting Conditions [NCT00602524]28 participants (Actual)Interventional2004-08-31Completed
Xerostomy Treatment in Patients With Sjogren's Syndrome in Chile :A Double Blind Control Trial Comparing Orally Pilocarpine Drops and Artificial Saliva [NCT00438048]Phase 476 participants (Actual)Interventional2006-11-30Completed
The Wearing-Off Period of Pharmacological Dilation: An Addendum to the Management of Anisocoria [NCT05238233]Phase 411 participants (Actual)Interventional2022-04-01Completed
Synergistic Use of Pilocarpine-Brimonidine-Oxymetazoline to Control Presbyopia Symptoms [NCT05006898]Phase 111 participants (Actual)Interventional2020-06-01Completed
Multicenter, Randomized, Double-Masked, Placebo-Controlled, Parallel Group Phase 2 Trial Evaluating the Safety and Efficacy of Pilocarpine Ophthalmic Topical Cream BID for the Treatment of Presbyopia [NCT05124275]Phase 2123 participants (Actual)Interventional2022-01-03Completed
Pharmacological Treatment of Presbyopia by Pilocarpine 1.25% Eye Drops [NCT05564832]Early Phase 175 participants (Anticipated)Interventional2022-08-01Recruiting
Efficacy of Cevimeline vs. Pilocarpine in the Secretion of Saliva [NCT01690052]15 participants (Actual)Interventional2009-01-31Completed
A Phase III Randomized Trial Comparing Oral Pilocarpine (Salagen) Versus Submandibular Salivary Gland Transfer Protocol, For the Prevention of Radiation (XRT) Induced Xerostomia in Head and Neck Cancer Patients [NCT00168181]Phase 3220 participants (Anticipated)Interventional2002-04-30Completed
Local Application of Pilocarpine for Relieving Dry Mouth Complaints: A Randomized Controlled Pilot Trial [NCT04195100]Early Phase 114 participants (Actual)Interventional2019-04-01Completed
The Diurnal and Nocturnal Effect of Pilocarpine on Intraocular Pressure and Ocular Perfusion Pressure [NCT02754570]27 participants (Actual)Interventional2016-07-31Completed
Effect of 0.1% Pilocarpine Mouthwash on Xerostomia : Double-blind, Randomized Controlled Trial [NCT01627626]60 participants (Actual)Interventional2011-08-31Completed
A Prospective Randomized Control Trial of Pilocarpine Use After Combined Cataract/Kahook Dual Blade Surgery [NCT03933631]Phase 3142 participants (Anticipated)Interventional2019-05-01Recruiting
Anterior Segment Imaging With Ultrahigh-resolution OCT in Patients With Glaucoma and Pseudoexfoliation Syndrome - a Pilot Study [NCT02865473]90 participants (Anticipated)Interventional2016-04-20Recruiting
(Study: Vertex IIS) A Study To Access the Effects of Ivacaftor on Wild Type CFTR-Open Probability (PO) In The Sweat Gland Secretory Coil [NCT02310789]8 participants (Actual)Interventional2015-07-31Completed
Effect of Pilocarpine in Patients With Xerostomia [NCT02982577]Phase 480 participants (Anticipated)Interventional2016-04-30Recruiting
A Double Blind Phase III Study of Oral Pilocarpine for Opioid-Induced Dry Mouth [NCT00003686]Phase 34 participants (Actual)Interventional1998-05-22Terminated(stopped due to Terminated due to poor accrual.)
A Prospective Randomized Control Trial of Pilocarpine Use After Combined Cataract/Trabectome Surgery [NCT04005079]Phase 30 participants (Actual)Interventional2019-06-05Withdrawn(stopped due to not performing Trabectomes)
Comparison of Pilocarpine, Brimonidine, Oxymetazoline, Hialuronic Acid, Bromfenac Ophthalmic Compound With Pilocarpine and Brimonidine to Improve Uncorrected Visual Acuity in Healthy Presbyopic Individuals [NCT05001243]Phase 111 participants (Anticipated)Interventional2021-08-10Recruiting
A Phase 1 Study to Investigate the Effect of Oral Doses of Pilocarpine on Salivary Secretion and Static Pupillometry in Healthy Subjects [NCT02447315]Phase 112 participants (Actual)Interventional2015-05-31Completed
Xerostomia in Patients With a Life-limiting Condition or Frailty: a Double-blind Placebo-controlled Randomized Clinical Trial [NCT05506137]Phase 3120 participants (Anticipated)Interventional2023-01-31Not yet recruiting
A Phase III Study to Test the Efficacy of the Prophylactic Use of Oral Pilocarpine to Reduce Hyposalivation and Mucositis Associated With Curative Radiation Therapy in Head and Neck Cancer Patients [NCT00003139]Phase 3249 participants (Actual)Interventional1998-03-31Completed
Implementation of a Non-invasive Version of the Imaging β-adrenergic-dependent Sweat Secretion Test: Value for Diagnosis and Efficacy of Target Therapies for Cystic Fibrosis [NCT03584841]120 participants (Anticipated)Interventional2017-03-31Recruiting
A Phase 3, Multicenter, Double-Masked, Randomized, Vehicle-Controlled, Parallel-Group Study Evaluating the Safety and Efficacy of AGN-190584 in Participants With Presbyopia [NCT03804268]Phase 3323 participants (Actual)Interventional2018-12-21Completed
Pilocarpine, Brimonidine, Oxymetazoline Ophthalmic Compound Safety and Efficacy in Patients With Presbyopia [NCT05006911]Phase 111 participants (Anticipated)Interventional2021-08-14Recruiting
Gender Differences in Renal Disease Progression: an Analysis of Potential Mechanisms Using Modern Radiological Techniques [NCT04085094]98 participants (Actual)Observational2017-05-30Completed
Effectiveness of Pilocarpine and Brimonidine to Improve Near Visual Acuity in Patients With Monofocal Intraocular Lenses [NCT03825081]Early Phase 133 participants (Anticipated)Interventional2019-01-21Recruiting
Oral Pilocarpine in the Treatment of the Dry Eye of Patients With Sjogrens Syndrome [NCT04470479]Phase 332 participants (Actual)Interventional2005-03-01Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00343382 (4) [back to overview]Average Vaginal Dryness Scores Via Area Under the Curve (AUC) Summary Statistics
NCT00343382 (4) [back to overview]Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) 3.0
NCT00343382 (4) [back to overview]Change From Baseline to Week 6 on the Impact of Vaginal Dryness for Activities of Daily Living Scores
NCT00343382 (4) [back to overview]Average AUC Summary Statistics for the Impact of Vaginal Dryness for Activities of Daily Living
NCT00656513 (8) [back to overview]Phase II: Treatment Compliance (Number of Compliant Patients)
NCT00656513 (8) [back to overview]Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
NCT00656513 (8) [back to overview]Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)
NCT00656513 (8) [back to overview]Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)
NCT00656513 (8) [back to overview]Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III)
NCT00656513 (8) [back to overview]Quality of Life (QOL) as Measured by the University of Washington Head and Neck Questionnaire (UWHNSS) Phase III
NCT00656513 (8) [back to overview]Phase III: Change From Baseline in Overall Xerostomia Burden at 9 Months
NCT00656513 (8) [back to overview]Phase II: Pecentage of Patients With Beneficial Treatment Response
NCT00762645 (2) [back to overview]Number of Patients With Peripheral Anterior Synechiae (PAS)
NCT00762645 (2) [back to overview]Mean Intraocular Pressure (IOP)
NCT01690052 (1) [back to overview]Change From Baseline in Saliva Production in ml.
NCT02310789 (2) [back to overview]Change Sweat Chloride Production
NCT02310789 (2) [back to overview]Change in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Dependent Sweat Rate
NCT02754570 (2) [back to overview]Change in Ocular Perfusion Pressure
NCT02754570 (2) [back to overview]Change in Intraocular Pressure From Baseline at Visit 3
NCT02935894 (8) [back to overview]Change in Pilocarpine-stimulated Sweat Lipid Mediator Concentrations Before and After Oral Ibuprofen Administration
NCT02935894 (8) [back to overview]Change in Plasma Ibuprofen Concentrations
NCT02935894 (8) [back to overview]Change in Plasma Lipid Mediator Concentrations Before and After Oral Ibuprofen Administration
NCT02935894 (8) [back to overview]Change in Sweat Ibuprofen Concentrations
NCT02935894 (8) [back to overview]Lower Back Sweat Lipid Mediator Concentrations Following Pilocarpine Stimulation
NCT02935894 (8) [back to overview]Volar Forearm Sweat Lipid Mediator Concentrations Following Exercise
NCT02935894 (8) [back to overview]Volar Forearm Sweat Lipid Mediator Concentrations Following Pilocarpine Stimulation
NCT02935894 (8) [back to overview]Anterior Distal Thigh Sweat Lipid Mediator Concentrations Following Pilocarpine Stimulation
NCT03804268 (13) [back to overview]Change From Baseline in Photopic, High-contrast, Binocular Distance-corrected Intermediate Visual Acuity (DCIVA) Letters at Day 30, Hour 3
NCT03804268 (13) [back to overview]Mean Change From Baseline in Mesopic NVPTQ Satisfaction Score at Day 30, Hour 3
NCT03804268 (13) [back to overview]Mean Change From Baseline in PICQ Impact Score at Day 30, Hour 3
NCT03804268 (13) [back to overview]Mean Change From Baseline in Presbyopia Impact and Coping Questionnaire (PICQ) Coping Score at Day 30, Hour 3
NCT03804268 (13) [back to overview]Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 1
NCT03804268 (13) [back to overview]Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 3
NCT03804268 (13) [back to overview]Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 3
NCT03804268 (13) [back to overview]Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 6
NCT03804268 (13) [back to overview]Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 10
NCT03804268 (13) [back to overview]Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 8
NCT03804268 (13) [back to overview]Mean Change From Baseline in Mesopic Near Vision Presbyopia Task-based Questionnaire (NVPTQ) Performance Score at Day 30, Hour 3
NCT03804268 (13) [back to overview]Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.25
NCT03804268 (13) [back to overview]Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.5
NCT03857542 (13) [back to overview]Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular DCNVA at Day 30, Hour 1
NCT03857542 (13) [back to overview]Mean Change From Baseline in Presbyopia Coping Questionnaire (PICQ) Coping Score at Day 30, Hour 3
NCT03857542 (13) [back to overview]Mean Change From Baseline in PICQ Impact Score at Day 30, Hour 3
NCT03857542 (13) [back to overview]Mean Change From Baseline in Mesopic NVPTQ Satisfaction Score at Day 30, Hour 3
NCT03857542 (13) [back to overview]Mean Change From Baseline in Mesopic Near Vision Presbyopia Task-based Questionnaire (NVPTQ) Performance Score at Day 30, Hour 3
NCT03857542 (13) [back to overview]Change From Baseline in Photopic, High-contrast, Binocular Distance-corrected Intermediate Visual Acuity (DCIVA) Letters at Day 30, Hour 3
NCT03857542 (13) [back to overview]Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.5
NCT03857542 (13) [back to overview]Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.25
NCT03857542 (13) [back to overview]Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 8
NCT03857542 (13) [back to overview]Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 10
NCT03857542 (13) [back to overview]Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular DCNVA, Without Losing More Than 5 Letters of Mesopic, High-Contrast, Binocular CDVA With the Same Refractive Correction at Day 30, Hour 3
NCT03857542 (13) [back to overview]Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular DCNVA at Day 30, Hour 6
NCT03857542 (13) [back to overview]Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 3
NCT04599933 (4) [back to overview]Percentage of Subjects With a ≥ 3-line Gain in BDCVA (Best Distance-Corrected Visual Acuity) at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m on Day 8, 1 Hour Post-Dose 1.
NCT04599933 (4) [back to overview]Percentage of Subjects With a ≥ 3-line Gain in BDCVA at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m on Day 8 at 1 Hour Post-Dose 2
NCT04599933 (4) [back to overview]Percentage of Subjects With a ≥ 3-line Gain in BDCVA at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m on Day 8 at 2 Hours Post-Dose 1
NCT04599933 (4) [back to overview]Percentage of Subjects With a ≥ 3-line Gain in BDCVA at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m on Day 8 at 2 Hours Post-dose 2
NCT04599972 (4) [back to overview]Percentage of Subjects With a ≥ 3-line Gain in BDCVA (Best Distance-Corrected Visual Acuity) at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m on Day 8, 1 Hour Post-Dose 1.
NCT04599972 (4) [back to overview]Percentage of Subjects With a ≥ 3-line Gain in BDCVA at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m on Day 8 at 1 Hour Post-Dose 2
NCT04599972 (4) [back to overview]Percentage of Subjects With a ≥ 3-line Gain in BDCVA at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m on Day 8 at 2 Hours Post-dose 2
NCT04599972 (4) [back to overview]Percentage of Subjects With a ≥ 3-line Gain in BDCVA at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m.
NCT04675151 (4) [back to overview]Percentage of Subjects With Improvement in DCIVA (Photopic) From Baseline
NCT04675151 (4) [back to overview]Percentage of Subjects With Improvement of ≥ 15 Letters in DCNVA (Photopic) at 1 Hour and With < 5 Letters of Loss in Photopic Binocular BCDVA From Baseline
NCT04675151 (4) [back to overview]Percent of Subjects With ≥ 15 Letters of Improvement in Photopic Binocular DCNVA
NCT04675151 (4) [back to overview]Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline
NCT04732195 (2) [back to overview]Amount of Sweat Collected
NCT04732195 (2) [back to overview]Sweat Chloride Concentration
NCT04983589 (4) [back to overview]Percentage of Participants Achieving 20/40 or Better in Mesopic, High-Contrast, Binocular DCNVA With No More Than a 5-Letter Loss in Mesopic CDVA With the Same Refractive Correction
NCT04983589 (4) [back to overview]Percentage of Participants Gaining 2 Lines or More in Mesopic, High-Contrast, Binocular DCNVA With No More Than a 5-Letter Loss in Mesopic CDVA With the Same Refractive Correction
NCT04983589 (4) [back to overview]Percentage of Participants Gaining 3 Lines or More in Mesopic, High-Contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) With No More Than 5-Letter Loss in Mesopic Corrected Distance Visual Acuity (CDVA) With the Same Refractive Correction
NCT04983589 (4) [back to overview]Percentage of Participants Gaining 3 Lines or More in Photopic, High-Contrast, Binocular DCNVA With No More Than a 5-Letter Loss in Photopic CDVA With the Same Refractive Correction
NCT05238233 (1) [back to overview]Number of Participants With Constricting Response to Pilocarpine 1% in the Pharmacologically Dilated Eye

Average Vaginal Dryness Scores Via Area Under the Curve (AUC) Summary Statistics

Vaginal dryness was measured by the numerical analogue scale at baseline and through the six weeks of treatment. The item scores was transformed into 0 to 100 scales with 0=poor quality of life (QOL) and 100=best possible QOL. The average AUC values were calculated by dividing 6 from AUC values for participants who completed item on all 6 weeks. If a participant completed the item at baseline, week 1, 2 and 3 but did not complete the item at week 4 to week 6, the AUC values of the item was prorated, which is (((AUC values * 6) / 3) / 6). The average pro-rated AUC for vaginal dryness scores was compared in each of the Pilocarpine arms against the collective placebo arm. (NCT00343382)
Timeframe: Baseline to Week 6

Interventionunits on a scale (Mean)
Collective Placebo63.6
Pilocarpine 2 Times Per Day55.8
Pilocarpine 4 Times Per Day66.0

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Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) 3.0

CTCAE Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death. (NCT00343382)
Timeframe: End of 6 weeks

,,
Interventionparticipants (Number)
Grade 1 or 2 rigorsGrade 1 or 2 urinary frequencyGrade 1 or 2 nauseaGrade 1 or 2 sweating
Collective Placebo212719
Pilocarpine 2 Times Per Day14211629
Pilocarpine 4 Times Per Day17292033

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Change From Baseline to Week 6 on the Impact of Vaginal Dryness for Activities of Daily Living Scores

The impact of vaginal dryness for activities of daily living (ADL) were measured by the numerical analogue scales at baseline and through the six weeks of treatment. The item scores was transformed into 0 to 100 scales with 0=poor quality of life (QOL) and 100=best possible QOL. The change from baseline scores was calculated by subtracting the baseline item scores from the scores at 6 week. (NCT00343382)
Timeframe: Baseline and Week 6

,,
Interventionunits on a scale (Mean)
Interfered with general activityInterfered with moodInterfered with normal workInterfered with relations with other peopleInterfered with sleepInterfered with enjoyment of life
Collective Placebo17.818.311.023.05.626.7
Pilocarpine 2 Times Per Day16.017.86.018.55.121.1
Pilocarpine 4 Times Per Day16.118.99.124.310.830.2

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Average AUC Summary Statistics for the Impact of Vaginal Dryness for Activities of Daily Living

The impact of vaginal dryness for activities of daily living (ADL) were measured by the numerical analogue scales at baseline and through the six weeks of treatment. The item scores was transformed into 0 to 100 scales with 0=poor quality of life (QOL) and 100=best possible QOL. The average AUC values were calculated by dividing 6 from AUC values for participants who completed item on all 6 weeks. If a participant completed the item at baseline, week 1, 2 and 3 but did not complete the item at week 4 to week 6, the AUC values of the item was prorated, which is (((AUC values * 6) / 3) / 6). The average pro-rated AUC scores was compared in each of the Pilocarpine arms against the collective placebo arm. (NCT00343382)
Timeframe: Baseline to Week 6

,,
Interventionunits on a scale (Mean)
Interfered with general activityInterfered with moodInterfered with normal workInterfered with relations with other peopleInterfered with sleepInterfered with enjoyment of life
Collective Placebo87.985.491.582.293.077.8
Pilocarpine 2 Times Per Day87.175.893.077.992.368.7
Pilocarpine 4 Times Per Day87.081.892.380.693.376.4

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Phase II: Treatment Compliance (Number of Compliant Patients)

Patients completing at least 19 out of 24 ALTENS therapy sessions were categorized as compliant. Fleming's two-stage was used, assuming a successful target compliance rate of 80%, statistical power of 0.87, and a type I error rate of 0.13. If fewer than 9 of the first 13 patients were compliant, then treatment delivery will be deemed not feasible. If there were between 9-12 compliant patients, the second stage analysis would be required to determine feasibility of treatment delivery. If all 13 patients are compliant, treatment delivery will immediately be deemed feasible. The second stage analysis required at least 31 compliant out of 39 overall patients for the treatment delivery to be deemed feasible. (NCT00656513)
Timeframe: Randomization to 12 weeks

InterventionParticipants (Count of Participants)
First StageSecond Stage (Overall)
ALTENS: Phase II1244

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Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)

Basal whole salivary production (WSP) was measured by expectoration weight, with one gram of saliva produced considered as one ml of saliva. WSP is expressed in ml/min calculated by dividing the measured weight or volume of WSP by five. Procedure: Patients refrain from eating, drinking, and smoking at least two hours prior to each measurement. For each measurement, patients are asked to expectorate continuously into a pre-weighed dry plastic container over a 5-minute period without swallowing. The collected saliva with the plastic container will be weighed (total weight) immediately after each collection. The total weight minus the weight of the container is the weight or volume of whole saliva collected. (NCT00656513)
Timeframe: Pre-treatment to 4, 6, 9 and 15 months from randomization

,
Interventionml/min (Median)
4 months6 months9 months15 months
ALTENS: Phase III00.020.040.192
Pilocarpine: Phase III000.0560.13

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Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III)

Symptom burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning. The domain score is the average of all responses on a given domain and can range from 0 to 4, with higher scores indicating increased symptom burden. Change in symptom burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the symptom burden. (NCT00656513)
Timeframe: Baseline, 4, 6, 9 and 15 months from randomization

,
Interventionunits on a scale (Median)
4-month Physical Functioning4-month Pain/Discomfort4-month Personal/Psychological Functioning4-month Social Functioning6-month Physical Functioning6-month Pain/Discomfort6-month Personal/Psychological Functioning6-month Social Functioning9-month Physical Functioning9-month Pain/Discomfort9-month Personal/Psychological Functioning9-month Social Functioning15-month Physical Functioning15-month Pain/Discomfort15-month Personal/Psychological Functioning15-month Social Functioning
ALTENS: Phase III-0.5-0.375-0.5-0.33-0.5-0.5-0.5-0.33-0.5-0.5-0.75-0.33-0.75-0.5-0.75-0.33
Pilocarpine: Phase III-0.5-0.25-0.250-0.5-0.25-0.25-0.33-0.5-0.25-0.5-0.66-0.5-0.5-0.50

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Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III)

Stimulated (citric acid primed) whole salivary production (WSP) was measured by expectoration weight, with one gram of saliva produced considered as one ml of saliva. WSP is expressed in ml/min calculated by dividing the measured weight or volume of WSP by five. Procedure: Patients refrain from eating, drinking, and smoking at least two hours prior to each measurement. Stimulation is elicited by asking patients to rinse 5 ml of 2% citric acid solution in the mouth for 15 seconds and then completely expectorating the citric acid. For each measurement, patients are asked to expectorate continuously into a pre-weighed dry plastic container over a 5-minute period without swallowing. The collected saliva with the plastic container will be weighed (total weight) immediately after each collection. The total weight minus the weight of the container is the weight or volume of whole saliva collected. (NCT00656513)
Timeframe: Baseline, 4, 6, 9 and 15 months from randomization

,
Interventionml/min (Median)
4 months6 months9 months15 months
ALTENS: Phase III0.20.400.600.20
Pilocarpine: Phase III0.030.20.990.3

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Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III)

Xerostomia burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4, with higher scores indicating increased xerostomia burden. Change in xerostomia burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the xerostomia burden. (NCT00656513)
Timeframe: Baseline, 4, 6, and 15 months from randomization

,
Interventionunits on a scale (Median)
4 months6 months15 months
ALTENS: Phase III-0.47-0.4-0.6
Pilocarpine: Phase III-0.27-0.33-0.47

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Quality of Life (QOL) as Measured by the University of Washington Head and Neck Questionnaire (UWHNSS) Phase III

The UWHNSS includes ten categories-pain, disfigurement, activity, recreation/entertainment, employment, eating, saliva, taste, speech, mucus/phlegm. Patient scores on the UWHNSS range from 0 to 100 with higher scores indicating declining quality of life. Change in total score was calculated by subtracting baseline from follow-up , thus a positive change score indicates a worsening while a negative change score indicates an improvement. (NCT00656513)
Timeframe: Baseline and 9 months from randomization.

Interventionunits on a scale (Median)
Pilocarpine: Phase III-3.64
ALTENS: Phase III-7.27

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Phase III: Change From Baseline in Overall Xerostomia Burden at 9 Months

Xerostomia burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4, with higher scores indicating increased xerostomia burden. Change in xerostomia burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the xerostomia burden. (NCT00656513)
Timeframe: Baseline (randomization) and 9 months

Interventionunits on a scale (Median)
Pilocarpine: Phase III-0.27
ALTENS: Phase III-0.53

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Phase II: Pecentage of Patients With Beneficial Treatment Response

This secondary objective was to evaluate the effect of ALTENS treatment on overall radiation-induced xerostomia burden by looking at treatment response. Treatment response was determined by a reduction of at least 20% from baseline to 6 months in the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4. Higher scores indicate increased xerostomia burden. This scale has high reproducibility and sensitivity. For the first and second stage analyses, 4 and 10 patients, respectively, must respond to treatment in order to proceed to the phase III component. (NCT00656513)
Timeframe: Pre-treatment and 6 months from registration

Interventionpercentage of participants (Number)
ALTENS: Phase II85.7

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Number of Patients With Peripheral Anterior Synechiae (PAS)

(NCT00762645)
Timeframe: Week 12 Visit

InterventionParticipants (Number)
Travoprost 0.004% (Travatan)0
Pilocarpine 1%0

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Mean Intraocular Pressure (IOP)

(NCT00762645)
Timeframe: 4PM at Week 12 Visit

Interventionmillimeters mercury (mm Hg) (Mean)
Travoprost 0.004% (Travatan)15.77
Pilocarpine 1%18.35

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Change From Baseline in Saliva Production in ml.

"The primary outcome measure was the change of stimulated and non-stimulated saliva in ml from the baseline record.~At each appointment (weekly), participants will provide 2 saliva samples to measure their current salivary output. The first measurement will be obtained by having the patient spit as much as he or she could into a cup for five minutes. The amount of saliva in ml will be recorded.~The second measurement will be obtained in a similar manner with the addition of having the patient chew on a block of unflavored wax. Patients will complete weekly questionnaires to help determine which side-effects they experience as they take the medications." (NCT01690052)
Timeframe: 4 weeks

,
Interventionml (Mean)
Unstimulated SalivaStimulated Saliva
Cevimeline1.415.31
Pilocarpine3.9310.34

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Change Sweat Chloride Production

Sweat chloride concentration was measured via the traditional sweat collection methods using the pilocarpine stimulation with the Macroduct device. (NCT02310789)
Timeframe: Up to 79 days

Interventionpercent change (Mean)
On ivacaftorOff Ivacaftor
Ivacaftor25.124.9

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Change in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Dependent Sweat Rate

CFTR-dependent sweat rate (C-sweat) was analyzed using a linear mixed model, combining on- and off-ivacaftor data. (NCT02310789)
Timeframe: Up to 79 days

Interventionpercent change (Mean)
1% β-adrenergic stimulationFull β-adrenergic stimulation
Ivacaftor16.456.60

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Change in Ocular Perfusion Pressure

Ocular perfusion pressure will calculated from the intraocular pressure and blood pressure measurements. At Baseline/Visit 2, intraocular pressure and blood pressure will be measured every 2 hours for a 24-hour period. At any point over the next 4 weeks, another 24-hour visit (Visit 3) will be performed. This time, a dose of pilocarpine 2% will be administered at 4 different times in addition to the latanoprost (PGA monotherapy). As before, intraocular pressure and blood pressure will be measured every 2 hours. 8 diurnal readings and 4 nocturnal readings were averaged separately during both Visit 2 for the PGA Monotherapy and Visit 3 for Pilocarpine+PGA (NCT02754570)
Timeframe: Two 24-hour visits: Baseline/Visit 2; Up to week 4/Visit 3

InterventionmmHg (Mean)
Visit 2: Diurnal Ocular Perfusion PressureVisit 2: Nocturnal Ocular Perfusion PressureVisit 2: Diurnal Systolic Blood PressureVisit 2: Nocturnal Systolic Blood PressureVisit 3: Diurnal Ocular Perfusion PressureVisit 3: Nocturnal Ocular Profusion PressureVisit 3: Diurnal Systolic Blood PressureVisit 3: Nocturnal Systolic Blood Pressure
Pilocarpine Group44.1237.2132.5125.844.337.1130.8122.7

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Change in Intraocular Pressure From Baseline at Visit 3

Subjects will be enrolled at the first visit. Patients already on latanoprost may proceed immediately with the second visit. Patients on a different prostaglandin analog medication will be switched to latanoprost for at least 6 weeks. At second visit, intraocular pressure and blood pressure will be measured every 2 hours for a 24-hour period. At any point over the next 4 weeks, another 24-hour visit will be performed. This time, a dose of pilocarpine 2% will be administered at 4 different times in addition to the latanoprost . As before, intraocular pressure and blood pressure will be measured every 2 hours. After visit 3, subjects will return to their prior treatment regimen. Change in the intraocular pressure from the second and the third visit will be determined. 8 diurnal readings and 4 nocturnal readings were averaged separately during both Visit 2 for the PGA Monotherapy and Visit 3 for Pilocarpine+PGA (NCT02754570)
Timeframe: Two 24-hour visits: Baseline/Visit 2; Up to week 4/Visit 3

InterventionmmHg (Mean)
Visit 2: Nocturnal PGAVisit 2: Diurnal PGAVisit 3: Nocturnal PGAVisit 3: Diurnal PGA
Pilocarpine Group21.118.220.017.1

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Change in Pilocarpine-stimulated Sweat Lipid Mediator Concentrations Before and After Oral Ibuprofen Administration

Approximately 100 lipid mediators will be measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Assayed lipid mediators include oxygenated lipids, endocannabinoids, and endocannabinoid-like molecules. (NCT02935894)
Timeframe: measured at four timepoints at study visit 4, detected lipid mediator concentrations for first timepoint reported

Interventionpicomoles per milliliter (Geometric Mean)
PGE1PGE213-HODE9-HODE13-HOTE9-HOTE20-HETE15-HETE12-HETE11-HETE8-HETE5-HETE15-HEPE12-HEPE17-HDoHE9,10-e-DiHO12,13-DiHOME9,10-DiHOME15,16-DiHODE12,13-DiHODE9,10-DiHODE14,15-DiHETrE11,12-DiHETrE5,6-DiHETrE17,18-DiHETESum TriHOMEs9(10)-EpO12(13)-EpOME9(10)-EpOME15(16)-EpODE12(13)-EpODE9(10)-EpODE13-KODE9-KODE12(13)-Ep-9-KODE10-Nitrooleate9-Nitrooleate10-NitrolinoleateOEALEANO-GlyNA-GlyOGLGAG
Single Group0.4532.7121.97.721.081.080.7420.3110.9650.08820.06180.1380.05760.07810.4658.41.893.611.490.3320.350.3410.2313.291.7631.72.810.4850.6570.4910.07030.1942.175.351.821.780.7290.2970.5860.04470.1560.062761.54.114.2

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Change in Plasma Ibuprofen Concentrations

Plasma concentration of ibuprofen prior to and 30 min, 2 hr and 4 hr after oral administration (NCT02935894)
Timeframe: measured at four timepoints at study visit 4

Interventionmicrograms per milliliter (Geometric Mean)
Prior to administration30 min after administration2 hr after administration4 hr after administration
Single Group018.848.333.8

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Change in Plasma Lipid Mediator Concentrations Before and After Oral Ibuprofen Administration

Approximately 100 lipid mediators will be measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Assayed lipid mediators include oxygenated lipids, endocannabinoids, and endocannabinoid-like molecules. (NCT02935894)
Timeframe: measured at four timepoints at study visit 4, detected lipid mediator concentrations for first timepoint reported

Interventionpicomoles per milliliter (Geometric Mean)
PGE1PGE2PGF2a13-HODE9-HODE13-HOTE9-HOTE15-HETE12-HETE11-HETE5-HETE17-HDoHE9,10-e-DiHO12,13-DiHOME9,10-DiHOME15,16-DiHODE12,13-DiHODE9,10-DiHODE14,15-DiHETrE11,12-DiHETrE5,6-DiHETrE17,18-DiHETE19,20-DiHDoPASum TriHOMEs9(10)-EpO12(13)-EpOME9(10)-EpOME15(16)-EpODE9(10)-EpODE13-KODE9-KODEOEALEAaLEADihomo GLA EAAEADEADHEANO-GlyNA-GlyOGLGAG
Single Group0.1260.1595.47238.771.561.190.8611.310.4080.4252.5510.44.134.44151.770.4581.171.110.40620.21.917.889.964.11.123.951.021.893.094.141.190.09680.1680.6270.2980.763.50.83339323820.7

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Change in Sweat Ibuprofen Concentrations

Sweat concentration of ibuprofen prior to and 30 min, 2 hr and 4 hr after oral administration (NCT02935894)
Timeframe: measured at four timepoints at study visit 4

Interventionmicrograms per milliliter (Geometric Mean)
Prior to administration30 min after administration2 hr after administration4 hr after administration
Single Group0000

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Lower Back Sweat Lipid Mediator Concentrations Following Pilocarpine Stimulation

Approximately 150 lipid mediators will be measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Assayed lipid mediators include oxygenated lipids, endocannabinoids and endocannabinoid-like molecules, and sphingolipids. (NCT02935894)
Timeframe: measured at study visit 1, detected lipid mediator concentrations reported

Interventionpicomoles per milliliter (Mean)
9-HODE13-HODE9-HOTrE13-HOTrE5-HETE8-HETE9-HETE11-HETE12-HETE15-HETE12-HEPE9,10-e-DiHO9,10-DiHOME12,13-DiHOME9,10-DiHODE12,13-DiHODE15,16-DiHODE5,6-DiHETrE8,9-DiHETrE11,12-DiHETrE14,15-DiHETrE9,10-EpOME12,13-EpOME9,10-EpODE12,13-EpODE15,16-EpODE9-KODE13-KODE12,13-Ep-9-KODE5-KETELTB510-Nitrooleate10-NitrolinoleatePGE1PGE2PGF2aPGE3Sum TriHOMEsPEASEAOEALEAaLEADihomo GLA EAAEADEA1-OG2-OG1-LG2-LG1-AG2-AGNO-GlyNA-GlyC14 CeramideC16 CeramideC18 CeramideC20 CeramideC24 Ceramide18:1 Sphingosine
Single Group17811.82.60.150.230.120.20.30.320.15362.62.20.380.340.552.80.10.280.341.61.60.280.20.491162.60.10.130.750.260.110.620.270.171247530.550.140.110.050.140.028300461102.6102.60.250.0270.491.70.340.330.418.1

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Volar Forearm Sweat Lipid Mediator Concentrations Following Exercise

Approximately 150 lipid mediators will be measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Assayed lipid mediators include oxygenated lipids, endocannabinoids and endocannabinoid-like molecules, and sphingolipids. (NCT02935894)
Timeframe: measured at study visit 1, detected lipid mediator concentrations reported

Interventionpicomoles per milliliter (Mean)
9-HODE13-HODE9-HOTrE13-HOTrE5-HETE8-HETE9-HETE11-HETE12-HETE15-HETE12-HEPE9,10-e-DiHO9,10-DiHOME12,13-DiHOME9,10-DiHODE12,13-DiHODE15,16-DiHODE5,6-DiHETrE8,9-DiHETrE11,12-DiHETrE14,15-DiHETrE9,10-EpOME12,13-EpOME9,10-EpODE12,13-EpODE15,16-EpODE9-KODE13-KODE12,13-Ep-9-KODE5-KETELTB510-Nitrooleate10-NitrolinoleatePGE1PGE2PGF2a15-deoxy PGJ2PGE3Sum TriHOMEsPEASEAOEALEAaLEADihomo GLA EAAEADEA1-OG2-OG1-LG2-LG1-AG2-AGNO-GlyNA-GlyC14 CeramideC16 CeramideC18 CeramideC20 CeramideC24 Ceramide18:1 Sphingosine
Single Group2.45.20.61.50.0230.140.0290.0120.040.0740.029213.12.80.560.31.90.0260.240.0220.0410.460.360.190.0190.821.50.893.40.020.0990.0740.0870.851.10.440.0460.1813014150.110.0190.00330.00230.0170.0151172.10.341.80.790.150.010.2310.290.360.884.9

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Volar Forearm Sweat Lipid Mediator Concentrations Following Pilocarpine Stimulation

Approximately 150 lipid mediators will be measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Assayed lipid mediators include oxygenated lipids, endocannabinoids and endocannabinoid-like molecules, and sphingolipids. (NCT02935894)
Timeframe: measured at study visit 1, 2 and 3; detected lipid mediator concentrations for study visit 1 reported

Interventionpicomoles per milliliter (Mean)
9-HODE13-HODE9-HOTrE13-HOTrE5-HETE8-HETE9-HETE11-HETE12-HETE15-HETE12-HEPE9,10-e-DiHO9,10-DiHOME12,13-DiHOME9,10-DiHODE12,13-DiHODE15,16-DiHODE5,6-DiHETrE8,9-DiHETrE11,12-DiHETrE14,15-DiHETrE9,10-EpOME12,13-EpOME9,10-EpODE12,13-EpODE15,16-EpODE9-KODE13-KODE12,13-Ep-9-KODE5-KETELTB510-Nitrooleate10-NitrolinoleatePGE1PGE2PGF2a15-deoxy PGJ2PGE3Sum TriHOMEsPEASEAOEALEAaLEADihomo GLA EAAEADEA1-OG2-OG1-LG2-LG1-AG2-AGNO-GlyNA-GlyC14 CeramideC16 CeramideC18 CeramideC20 CeramideC24 Ceramide18:1 Sphingosine
Single Group20462.23.50.10.230.120.150.850.430.086854.43.40.850.52.75.30.730.510.651.70.960.550.123.5147.23.70.0250.10.0960.110.242.10.140.0330.13577.97.90.320.0430.00470.00220.0190.178701903002.314150.480.0171.46.61.225.715

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Anterior Distal Thigh Sweat Lipid Mediator Concentrations Following Pilocarpine Stimulation

Approximately 150 lipid mediators will be measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Assayed lipid mediators include oxygenated lipids, endocannabinoids and endocannabinoid-like molecules, and sphingolipids. (NCT02935894)
Timeframe: measured at study visit 2, detected lipid mediator concentrations reported

Interventionpicomoles per milliliter (Mean)
9-HODE13-HODE9-HOTrE13-HOTrE5-HETE8-HETE9-HETE11-HETE12-HETE15-HETE12-HEPE9,10-e-DiHO9,10-DiHOME12,13-DiHOME9,10-DiHODE12,13-DiHODE15,16-DiHODE5,6-DiHETrE8,9-DiHETrE11,12-DiHETrE14,15-DiHETrE9,10-EpOME12,13-EpOME9,10-EpODE12,13-EpODE15,16-EpODE9-KODE13-KODE12,13-Ep-9-KODE5-KETELTB510-Nitrooleate10-NitrolinoleatePGE1PGE2PGF2aPGE3Sum TriHOMEsPEASEAOEALEAaLEADihomo GLA EAAEADEA1-OG2-OG1-LG2-LG1-AG2-AGNO-GlyNA-GlyC14 CeramideC16 CeramideC18 CeramideC20 CeramideC24 Ceramide18:1 Sphingosine
Single Group19481.85.20.0670.170.120.120.310.260.13352.92.40.460.70.992.70.620.190.191.71.60.80.250.95219.33.30.040.0880.120.160.180.360.440.153618180.310.0780.0220.000370.0130.05320037812.1134.20.230.020.241.50.310.3612.2

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Change From Baseline in Photopic, High-contrast, Binocular Distance-corrected Intermediate Visual Acuity (DCIVA) Letters at Day 30, Hour 3

Visual acuity for intermediate (66 cm) target was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. MMRM was used for analyses. (NCT03804268)
Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Interventionletters read correctly (Least Squares Mean)
Vehicle3.1
Pilocarpine HCl Ophthalmic Solution6.6

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Mean Change From Baseline in Mesopic NVPTQ Satisfaction Score at Day 30, Hour 3

NVPTQ had 12 questions on 4 reading tasks(reading a paragraph from book, excerpts from an article in newspaper, portion of a nutrition label, and a section from restaurant menu). Participants completed specific reading tasks under mesopic conditions without any near-vision correction and answered 3 questions for each task, rating their vision-related reading ability as 0=I could not read any text due to problems seeing up close to 5=excellent; impact of squinting on performance as 0=No, I did not squint, 1=Yes, squinting helped me read some/all text, 2=Yes, but I still could not read any of the text; and satisfaction as 0=very dissatisfied,1=dissatisfied,2=neither satisfied nor dissatisfied,3=satisfied, 4=very satisfied. The score based on satisfaction items=(Book testlet+Newspaper testlet+Menu testlet+Nutrition Label testlet)/(testlets with non-missing responses) for a total possible score of 0 to 4. Higher scores=better outcomes; a positive change from Baseline=higher satisfaction. (NCT03804268)
Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Interventionscore on a scale (Least Squares Mean)
Vehicle0.6
Pilocarpine HCl Ophthalmic Solution1.4

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Mean Change From Baseline in PICQ Impact Score at Day 30, Hour 3

PICQ had 20 questions about impact experienced by participants due to their problems seeing up over past 7 days. PICQ Impact domain had 6 items: Item 9:Rely on others,15:rest eyes,16:Feel older,17:Feel self-conscious,19:Take longer to complete a task,20:Inconvenient. First 5 impacts items included response categories: 0=never to 4=all the time. Item 20 had response categories: 0=not at all to 4=extremely. Item 9 included an additional response category with a value of 9 to indicate question was not applicable to participant and the responses were assigned missing values. PICQ Impacts Score=[(Item9+Item15+Items16,17Testlet+Item19+Item20)/(nonmissing responses to 5 components of impacts score)] where Items 16,17 Testlet=(Item16+Item17)/non-missing responses to Items 16 and 17. PICQ Impact score ranges from 0 to 4; with 0=least amount of impacts to 4=greatest amount of impacts. Higher scores correspond to poorer outcomes. A negative change from Baseline=improvement. (NCT03804268)
Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Interventionscore on a scale (Least Squares Mean)
Vehicle-0.4
Pilocarpine HCl Ophthalmic Solution-0.7

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Mean Change From Baseline in Presbyopia Impact and Coping Questionnaire (PICQ) Coping Score at Day 30, Hour 3

PICQ=20 questions about impact experienced by participants due to their problems over past 7 days.PICQ Coping domain had 8 items: 1:Normal-sized text,2:Small-sized text,3:Information on a computer,4:Information on a cell phone,5:Increase font size,6:Use glasses to read close,12:Hold reading materials farther out/closer,13:Squint to read. Each item had response categories:0=never to 4=all the time. Items 3, 4, 5, and 6 had additional response categories with values of 9/10 to indicate the question is not applicable to participant and were assigned missing values.PICQ Coping Score:(Item 1,2 Testlet+Item 3,4 Testlet+Item 5+Item 6+Item 12+Item 13)/non-missing responses to the 6 components of coping score where Items 1,2 Testlet=(Item1+Item2)/non-missing responses to Items 1,2;Items 3,4 Testlet=(Item3+Item4)/non-missing responses to Items 3, 4. Score ranges:0=to least amount of coping to 4=greatest amount of coping. Higher scores=poorer outcome; a negative change from Baseline=improvement. (NCT03804268)
Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Interventionscore on a scale (Least Squares Mean)
Vehicle-0.5
Pilocarpine HCl Ophthalmic Solution-1.0

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Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 1

Visual acuity for near (40 cm) target was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. Percentage of participants achieving 20/40 or better in photopic, high-contrast, binocular, DCNVA are reported. (NCT03804268)
Timeframe: Day 30 (Hour 1)

Interventionpercentage of participants (Number)
Vehicle73.9
Pilocarpine HCl Ophthalmic Solution92.5

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Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 3

Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. Percentage of participants achieving 20/40 or better in photopic, high-contrast, binocular, DCNVA are reported. (NCT03804268)
Timeframe: Day 30 (Hour 3)

Interventionpercentage of participants (Number)
Vehicle71.9
Pilocarpine HCl Ophthalmic Solution84.5

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Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 3

Visual acuity for near (40 centimeters (cm)) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter (cd/m^2) measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported. (NCT03804268)
Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Interventionpercentage of participants (Number)
Vehicle8.1
Pilocarpine HCl Ophthalmic Solution30.7

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Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 6

Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported. (NCT03804268)
Timeframe: Baseline (Day 1) to Day 30 (Hour 6)

Interventionpercentage of participants (Number)
Vehicle8.8
Pilocarpine HCl Ophthalmic Solution18.4

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Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 10

Visual acuity for near (40cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast, binocular DCNVA are reported. (NCT03804268)
Timeframe: Baseline (Day1) to Day 30 (Hour 10)

Interventionpercentage of participants (Number)
Vehicle8.6
Pilocarpine HCl Ophthalmic Solution7.5

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Percentage of Participants Gaining 3-lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 8

Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported. (NCT03804268)
Timeframe: Baseline (Day 1) to Day 30 (Hour 8)

Interventionpercentage of participants (Number)
Vehicle8.5
Pilocarpine HCl Ophthalmic Solution10.6

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Mean Change From Baseline in Mesopic Near Vision Presbyopia Task-based Questionnaire (NVPTQ) Performance Score at Day 30, Hour 3

NVPTQ had 12 questions on 4 reading tasks(reading a paragraph from book, excerpts from an article in newspaper, portion of a nutrition label, and a section from restaurant menu). Participants completed specific reading tasks under mesopic conditions without any near-vision correction and answered 3 questions for each task, rating their vision-related reading ability as 0=I could not read any text due to problems seeing up close,1=poor,2=fair,3=good,4=very good,5=excellent;impact of squinting on performance as 0=No,I did not squint, 1=Yes,squinting helped me read some/all text, 2=Yes,but I still could not read any of the text; and satisfaction as 0=very dissatisfied to 4=very satisfied. The score based on vision related ability and impact of squinting=(Book testlet+Newspaper testlet+Menu testlet+Nutrition Label testlet)/(testlets with non-missing responses), total possible score of 0-5. Higher scores=better outcomes;positive change from Baseline=improved performance(reading ability). (NCT03804268)
Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Interventionscore on a scale (Least Squares Mean)
Vehicle0.6
Pilocarpine HCl Ophthalmic Solution1.4

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Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.25

Visual acuity for near (40 cm) target was measured in mesopic conditions. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. MMRM was used for analyses. (NCT03804268)
Timeframe: Baseline (Day 1) to Day 30 (Hour 0.25)

Interventionletters correctly read (Least Squares Mean)
Vehicle3.7
Pilocarpine HCl Ophthalmic Solution6.3

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Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.5

Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. A positive change from Baseline indicates improvement in visual acuity. Mixed effect model for repeated measures (MMRM) was used for analyses. (NCT03804268)
Timeframe: Baseline (Day 1) to Day 30 (Hour 0.5)

Interventionletters read correctly (Least Squares Mean)
Vehicle4.2
Pilocarpine HCl Ophthalmic Solution9.3

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Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular DCNVA at Day 30, Hour 1

Visual acuity for near (40 cm) target was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. (NCT03857542)
Timeframe: Day 30 (Hour 1)

Interventionpercentage of participants (Number)
Vehicle82.8
Pilocarpine HCl Ophthalmic Solution92.7

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Mean Change From Baseline in Presbyopia Coping Questionnaire (PICQ) Coping Score at Day 30, Hour 3

PICQ=20 questions about impact experienced by participants due to their problems over past 7 days.PICQ Coping domain had 8 items: 1:Normal-sized text,2:Small-sized text,3:Information on a computer,4:Information on a cell phone,5:Increase font size,6:Use glasses to read close,12:Hold reading materials farther out/closer,13:Squint to read. Each item had response categories:0=never to 4=all the time. Items 3, 4, 5, and 6 had additional response categories with values of 9/10 to indicate the question is not applicable to participant and were assigned missing values.PICQ Coping Score:(Item 1,2 Testlet+Item 3,4 Testlet+Item 5+Item 6+Item 12+Item 13)/non-missing responses to the 6 components of coping score where Items 1,2 Testlet=(Item1+Item2)/non-missing responses to Items 1,2;Items 3,4 Testlet=(Item3+Item4)/non-missing responses to Items 3, 4. Score ranges:0=to least amount of coping to 4=greatest amount of coping. Higher scores=poorer outcome; a negative change from Baseline=improvement. (NCT03857542)
Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Interventionscore on a scale (Least Squares Mean)
Vehicle-0.5
Pilocarpine HCl Ophthalmic Solution-0.9

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Mean Change From Baseline in PICQ Impact Score at Day 30, Hour 3

PICQ had 20 questions about impact experienced by participants due to their problems seeing up over past 7 days. Impact domain of PICQ has 6 items:Item9:Rely on others,Item15:rest eyes,Item16:Feel older,Item17:Feel self-conscious,Item19:Take longer to complete task,Item20:Inconvenient.First 5 impacts items include response ranges from 0=never to 4=all of time. Item20 ranged from 0=Not at all,to 4=Extremely. Item9 included an additional response category, labeled with value of 9 to indicate question is not applicable because participant did not have opportunity to experience impact responses are assigned missing values. PICQ Impacts Score=[(Items 9+15+16&17 Testlet+Item19+Item20)/(nonmissing responses to 5 components of impacts score)] where Items 16&17 Testlet=(Items16+17)/non-missing responses to Items16 and 17. PICQ Impact score ranged 0-4, 0=least amount of impacts,4=greatest amount of impacts. Higher scores correspond to poorer outcomes; negative change from Baseline=improvement. (NCT03857542)
Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Interventionscore on a scale (Least Squares Mean)
Vehicle-0.4
Pilocarpine HCl Ophthalmic Solution-0.7

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Mean Change From Baseline in Mesopic NVPTQ Satisfaction Score at Day 30, Hour 3

NVPTQ had 12 questions on 4 reading tasks(reading a paragraph from book, excerpts from a newspaper article, portion of a nutrition label, and a section from restaurant menu). Participants completed specific reading tasks under mesopic conditions without any near-vision correction and answered 3 questions for each task, related as 0=I could not read any text due to problems seeing up close,1=poor,2=fair,3=good,4=very good,5=excellent; impact of squinting as 0=No, I did not squint, 1=Yes, squinting helped me read some/all text, 2=Yes, but I still could not read any of the text; and satisfaction as 0=very dissatisfied to 4=very satisfied. NVPTQ Satisfaction Score=(Book testlet+Newspaper testlet+Menu testlet+Nutrition Label testlet)/(testlets with non-missing responses)based on satisfaction items for a total possible score of 0 to 4. Higher scores=better outcomes; a positive change from Baseline indicates higher satisfaction. (NCT03857542)
Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Interventionscore on a scale (Least Squares Mean)
Vehicle0.5
Pilocarpine HCl Ophthalmic Solution1.2

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Mean Change From Baseline in Mesopic Near Vision Presbyopia Task-based Questionnaire (NVPTQ) Performance Score at Day 30, Hour 3

NVPTQ had 12 questions on 4 reading tasks(reading a paragraph from book, excerpts from a newspaper article, portion of a nutrition label, and a section from restaurant menu). Participants completed specific reading tasks under mesopic conditions without any near-vision correction and answered 3 questions for each task, rated as 0=I could not read any text due to problems seeing up close,1=poor,2=fair,3=good,4=very good,5=excellent; impact of squinting as 0=No,I did not squint, 1=Yes, squinting helped me read some/all text, 2=Yes,but I still could not read any of the text; and satisfaction as 0=very dissatisfied to 4=very satisfied. The score based on vision-related ability and impact of squinting=(Book testlet+Newspaper testlet+Menu testlet+Nutrition Label testlet)/(testlets with non-missing responses), total possible score of 0-5. Higher scores=better outcomes;positive change from Baseline=improved performance (reading ability). (NCT03857542)
Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Interventionscore on a scale (Least Squares Mean)
Vehicle0.5
Pilocarpine HCl Ophthalmic Solution1.3

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Change From Baseline in Photopic, High-contrast, Binocular Distance-corrected Intermediate Visual Acuity (DCIVA) Letters at Day 30, Hour 3

Visual acuity for intermediate (66 cm) target was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. MMRM was used for the analysis. (NCT03857542)
Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Interventionnumber of letters read correctly (Least Squares Mean)
Vehicle2.9
Pilocarpine HCl Ophthalmic Solution6.4

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Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.5

Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as lighting 3.2 to 3.5 cd/m^2 measured at the target. Mixed effect model for repeated measures (MMRM) was used for the analysis. (NCT03857542)
Timeframe: Baseline (Day 1) to Day 30 (Hour 0.5)

Interventionletters read correctly (Least Squares Mean)
Vehicle4.7
Pilocarpine HCl Ophthalmic Solution8.8

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Change From Baseline in Mesopic, High-contrast, Binocular DCNVA Letters at Day 30, Hour 0.25

Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. MMRM was used for the analysis. (NCT03857542)
Timeframe: Baseline (Day 1) to Day 30 (Hour 0.25)

Interventionletters read correctly (Least Squares Mean)
Vehicle3.9
Pilocarpine HCl Ophthalmic Solution 1.25%6.5

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Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 8

Visual acuity for near (40 cm) was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. Baseline for efficacy was defined as the last non-missing efficacy assessment before the first dose of study intervention. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported. (NCT03857542)
Timeframe: Baseline (Day 1) to Day 30 (Hour 8)

Interventionpercentage of participants (Number)
Vehicle8.6
Pilocarpine HCl Ophthalmic Solution14.5

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Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular, DCNVA at Day 30, Hour 10

Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast, binocular DCNVA are reported. (NCT03857542)
Timeframe: Baseline (Day 1) to Day 30 (Hour 10)

Interventionpercentage of participants (Number)
Vehicle8.7
Pilocarpine HCl Ophthalmic Solution12.6

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Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular DCNVA, Without Losing More Than 5 Letters of Mesopic, High-Contrast, Binocular CDVA With the Same Refractive Correction at Day 30, Hour 3

Visual acuity for near (40 centimeter (cm)) and distance (4 meter (m)) targets were measured in mesopic conditions using an eye chart. High contrast corrected distance visual acuity (CDVA) was assessed binocularly (in each eye) using the provided visual acuity charts for distance vision in a room with mesopic lighting conditions measured at the target. Forced choice letter by-letter scoring was used for each test and the total number of correct letters or the highest value (number) of the grid identified (as applicable) were recorded. Mesopic condition was defined as low lighting 3.2 to 3.5 candelas per square meter (cd/m^2) measured at the target. DCNVA= distance-corrected near visual acuity. (NCT03857542)
Timeframe: Baseline (Day 1) to Day 30 (Hour 3)

Interventionpercentage of participants (Number)
Vehicle10.8
Pilocarpine HCl Ophthalmic Solution26.0

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Percentage of Participants Gaining 3 Lines or More in Mesopic, High-contrast, Binocular DCNVA at Day 30, Hour 6

Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Mesopic condition was defined as low lighting 3.2 to 3.5 cd/m^2 measured at the target. Percentage of participants with 3 lines or more improvement from Baseline in mesopic, high-contrast DCNVA are reported. (NCT03857542)
Timeframe: Baseline (Day 1) to Day 30 (Hour 6)

Interventionpercentage of participants (Number)
Vehicle9.9
Pilocarpine HCl Ophthalmic Solution16.3

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Percentage of Participants Achieving 20/40 or Better in Photopic, High-contrast, Binocular, DCNVA at Day 30, Hour 3

Visual acuity for near (40 cm) targets was measured in photopic conditions using an eye chart. Photopic condition was defined as high lighting ≥80 cd/m^2 measured at the target. (NCT03857542)
Timeframe: Day 30 (Hour 3)

Interventionpercentage of participants (Number)
Vehicle77.8
Pilocarpine HCl Ophthalmic Solution90.2

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Percentage of Subjects With a ≥ 3-line Gain in BDCVA (Best Distance-Corrected Visual Acuity) at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m on Day 8, 1 Hour Post-Dose 1.

"The primary end-point was measured on Day 8, 1 hour post first CSF-1 dose, as the number of participants who are responders to the treatment.~A responder was defined as as subject with a ≥ 3-line gain in BDCVA (Best Distance-Corrected Visual Acuity) at 40cm and no loss in BDCVA ≥ 5 letters at 4m." (NCT04599933)
Timeframe: Baseline (Day 1) to Day 8 (1 hour post-Dose 1)

InterventionParticipants (Count of Participants)
CSF-160
Vehicle26

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Percentage of Subjects With a ≥ 3-line Gain in BDCVA at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m on Day 8 at 1 Hour Post-Dose 2

The key secondary endpoints were measured on Day 8 at different time points and were the percentage of subjects with a ≥ 3-line (15-letter) gain, from baseline, in BDCVA at 40 cm (Precision Vision Chart) and no loss in BDCVA ≥ 5 letters (ETDRS chart at 4 m) in the study eye. (NCT04599933)
Timeframe: Baseline (Day 1) to Day 8 (1 hour post-Dose 2)

InterventionParticipants (Count of Participants)
CSF-174
Vehicle24

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Percentage of Subjects With a ≥ 3-line Gain in BDCVA at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m on Day 8 at 2 Hours Post-Dose 1

The key secondary endpoints were measured on Day 8 at different time points and were the percentage of subjects with a ≥ 3-line (15-letter) gain, from baseline, in BDCVA at 40 cm (Precision Vision Chart) and no loss in BDCVA ≥ 5 letters (ETDRS chart at 4 m) in the study eye. (NCT04599933)
Timeframe: Baseline (Day 1) to Day 8 (2 hours post-Dose 1)

InterventionParticipants (Count of Participants)
CSF-161
Vehicle26

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Percentage of Subjects With a ≥ 3-line Gain in BDCVA at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m on Day 8 at 2 Hours Post-dose 2

The key secondary endpoints were measured on Day 8 at different time points and were the percentage of subjects with a ≥ 3-line (15-letter) gain, from baseline, in BDCVA at 40 cm (Precision Vision Chart) and no loss in BDCVA ≥ 5 letters (ETDRS chart at 4 m) in the study eye. (NCT04599933)
Timeframe: Baseline (Day 1) to Day 8 (2 hours post-Dose 2)

InterventionParticipants (Count of Participants)
CSF-160
Vehicle23

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Percentage of Subjects With a ≥ 3-line Gain in BDCVA (Best Distance-Corrected Visual Acuity) at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m on Day 8, 1 Hour Post-Dose 1.

"The primary end-point was measured on Day 8, 1 hour post first CSF-1 dose, as the number of participants who are responders to the treatment.~A responder was defined as as subject with a ≥ 3-line gain in BDCVA (Best Distance-Corrected Visual Acuity) at 40cm and no loss in BDCVA ≥ 5 letters at 4m." (NCT04599972)
Timeframe: Baseline (Day 1) to Day 8 (1 hour post-Dose 1)

InterventionParticipants (Count of Participants)
CSF-164
Vehicle32

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Percentage of Subjects With a ≥ 3-line Gain in BDCVA at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m on Day 8 at 1 Hour Post-Dose 2

The key secondary endpoints were measured on Day 8 at different time points and were the percentage of subjects with a ≥ 3-line (15-letter) gain, from baseline, in BDCVA at 40 cm (Precision Vision Chart) and no loss in BDCVA ≥ 5 letters (ETDRS chart at 4 m) in the study eye. (NCT04599972)
Timeframe: Baseline (Day 1) to Day 8 (1 hour post Dose 2)

InterventionParticipants (Count of Participants)
CSF-180
Vehicle25

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Percentage of Subjects With a ≥ 3-line Gain in BDCVA at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m on Day 8 at 2 Hours Post-dose 2

The key secondary endpoints were measured on Day 8 at different time points and were the percentage of subjects with a ≥ 3-line (15-letter) gain, from baseline, in BDCVA at 40 cm (Precision Vision Chart) and no loss in BDCVA ≥ 5 letters (ETDRS chart at 4 m) in the study eye. (NCT04599972)
Timeframe: Baseline (Day 1) to Day 8 (2 hours post Dose 2)

InterventionParticipants (Count of Participants)
CSF-171
Vehicle29

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Percentage of Subjects With a ≥ 3-line Gain in BDCVA at 40cm and no Loss in BDCVA ≥ 5 Letters at 4m.

The key secondary endpoints were measured on Day 8 at different time points and were the percentage of subjects with a ≥ 3-line (15-letter) gain, from baseline, in BDCVA at 40 cm (Precision Vision Chart) and no loss in BDCVA ≥ 5 letters (ETDRS chart at 4 m) in the study eye. (NCT04599972)
Timeframe: Baseline (Day 1) to Day 8 (2 hours post-Dose 1)

InterventionParticipants (Count of Participants)
CSF-162
Vehicle31

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Percentage of Subjects With Improvement in DCIVA (Photopic) From Baseline

The percentage of subjects with improvement in DCIVA (photopic) from Baseline of ≥ 5, ≥ 10, and ≥ 15 letters (NCT04675151)
Timeframe: Visit 2 at 1 hour, at 3 hours, and at 6 hours

,,,
Interventionpercentage with improvement (Number)
% of subjects with improvement of ≥ 5 letters from baseline at 1 hour% of subjects with improvement of ≥ 10 letters from baseline at 1 hour% of subjects with improvement of ≥ 15 letters from baseline at 1 hour% of subjects with improvement of ≥ 5 letters from baseline at 3 hours% of subjects with improvement of ≥ 10 letters from baseline at 3 hours% of subjects with improvement of ≥ 15 letters from baseline at 3 hours% of subjects with improvement of ≥ 5 letters from baseline at 6 hours% of subjects with improvement of ≥ 10 letters from baseline at 6 hours% of subjects with improvement of ≥ 15 letters from baseline at 6 hours
POS 0.75% First, Then LDP 0.4%86.048.814.069.841.918.672.130.214.0
POS 0.75% First, Then LDP Vehicle46.723.310.043.330.010.056.716.710.0
POS Vehicle First, Then LDP 0.4%71.045.222.667.741.922.638.729.012.9
POS Vehicle First, Then LDP Vehicle56.825.04.550.025.04.547.718.24.5

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Percentage of Subjects With Improvement of ≥ 15 Letters in DCNVA (Photopic) at 1 Hour and With < 5 Letters of Loss in Photopic Binocular BCDVA From Baseline

The percentage of subjects with improvement of ≥ 15 letters in DCNVA (photopic) at 1 hour and with < 5 letters of loss in photopic binocular BCDVA from Baseline (NCT04675151)
Timeframe: Visit 2 at 1 hour

Intervention% of subjects with improvement (Number)
POS 0.75% First, Then LDP 0.4%60.5
POS 0.75% First, Then LDP Vehicle30.0
POS Vehicle First, Then LDP 0.4%41.9
POS Vehicle First, Then LDP Vehicle27.93

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Percent of Subjects With ≥ 15 Letters of Improvement in Photopic Binocular DCNVA

The primary efficacy endpoint was the percent of subjects with ≥ 15 letters of improvement in photopic binocular DCNVA on Visit 2 at 1 hour with POS + LDP compared to placebo alone. The improvement in binocular DCNVA for each subject was relative to the subject's own baseline value (Visit 1). (NCT04675151)
Timeframe: Visit 2 at 1 hour

Interventionpercentage of subjects with ≥ 15 letters (Number)
POS 0.75% First, Then LDP 0.4%60.5
POS 0.75% First, Then LDP Vehicle30.0
POS Vehicle First, Then LDP 0.4%45.2
POS Vehicle First, Then LDP Vehicle27.3

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Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline

The percentage of subjects with improvement of ≥ 5, ≥ 10, and ≥ 15 letters in DCNVA (photopic) from Baseline at 0.5 hours, at 2 hours, at 3 hours, at 4 hours, and at 6 hours (NCT04675151)
Timeframe: Visit 2 at 0.5 hours, at 2 hours, at 3 hours, at 4 hours, and at 6 hours

,,,
Interventionpercentage of subjects with improvement (Number)
% of subjects with improvement of ≥ 5 letters from baseline at 0.5 hours% of subjects with improvement of ≥ 10 letters from baseline at 0.5 hours% of subjects with improvement of ≥ 15 letters from baseline at 0.5 hours% of subjects with improvement of ≥ 5 letters from baseline at 2 hours% of subjects with improvement of ≥ 10 letters from baseline at 2 hours% of subjects with improvement of ≥ 15 letters from baseline at 2 hours% of subjects with improvement of ≥ 5 letters from baseline at 3 hours% of subjects with improvement of ≥ 10 letters from baseline at 3 hours% of subjects with improvement of ≥ 15 letters from baseline at 3 hours% of subjects with improvement of ≥ 5 letters from baseline at 4 hours% of subjects with improvement of ≥ 10 letters from baseline at 4 hours% of subjects with improvement of ≥ 15 letters from baseline at 4 hours% of subjects with improvement of ≥ 5 letters from baseline at 6 hours% of subjects with improvement of ≥ 10 letters from baseline at 6 hours% of subjects with improvement of ≥ 15 letters from baseline at 6 hours
POS 0.75% First, Then LDP 0.4%88.476.760.588.481.462.895.367.446.595.367.446.588.467.437.2
POS 0.75% First, Then LDP Vehicle86.750.033.393.360.026.783.360.026.783.360.030.086.760.036.7
POS Vehicle First, Then LDP 0.4%74.254.825.883.971.041.983.964.548.483.951.632.371.054.822.6
POS Vehicle First, Then LDP Vehicle70.552.315.970.545.518.272.743.220.575.050.020.572.750.018.2

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Amount of Sweat Collected

Sweat weight in mg collected after application of Pilocarpine Microneedle patch was compared to the forearm of healthy adult subjects with that of standard of care method using pilocarpine iontophoresis (NCT04732195)
Timeframe: 45 min Post-intervention

Interventionmg (Mean)
Pilocarpine Microneedle Patch Method41.2
Pilocarpine Iontophoresis Method43.8

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Sweat Chloride Concentration

Sweat chloride concentrations will be measured from the sweat samples obtained from the application of Pilocarpine Microneedle patch to the forearm of healthy adult subjects and compare them with measurements from standard of care method using pilocarpine iontophoresis. (NCT04732195)
Timeframe: 45 min Post-intervention

Interventionmmol/L (Mean)
Pilocarpine Microneedle Patch Method31.2
Pilocarpine Iontophoresis Method24.0

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Percentage of Participants Achieving 20/40 or Better in Mesopic, High-Contrast, Binocular DCNVA With No More Than a 5-Letter Loss in Mesopic CDVA With the Same Refractive Correction

Visual acuity for near (40 cm) target was measured in mesopic conditions using an eye chart. Both near vision and distance vision were measured to evaluate the effect of AGN-190584. A participant who achieved 20/40 or better in mesopic, high contrast, binocular DCNVA with no more than 5-letter loss in mesopic CDVA with the same refractive correction was regarded as a responder at that visit/timepoint. A participant with missing data was regarded as a non-responder. (NCT04983589)
Timeframe: 3 hours after second dose on Day 14

Interventionpercentage of participants (Number)
Vehicle24.1
AGN-19058444.7

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Percentage of Participants Gaining 2 Lines or More in Mesopic, High-Contrast, Binocular DCNVA With No More Than a 5-Letter Loss in Mesopic CDVA With the Same Refractive Correction

Visual acuity for near (40 centimeter [cm]) and distance (4 meter [m]) targets were measured in mesopic conditions using an eye chart. High contrast corrected distance visual acuity (CDVA) was assessed binocularly (in each eye) using the provided visual acuity charts for distance vision in a room with photopic lighting conditions (10 to 11 lux) measured at the target. Both near vision and distance vision were measured to evaluate the effect of AGN-190584. A participant who gained 2 lines or more in mesopic, high contrast, binocular DCNVA with no more than 5-letter loss in mesopic CDVA with the same refractive correction was regarded as a responder at that visit/timepoint. A participant with missing data was regarded as a non-responder. (NCT04983589)
Timeframe: 3 hours after second dose on Day 14

Interventionpercentage of participants (Number)
Vehicle25.9
AGN-19058460.5

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Percentage of Participants Gaining 3 Lines or More in Mesopic, High-Contrast, Binocular Distance-Corrected Near Visual Acuity (DCNVA) With No More Than 5-Letter Loss in Mesopic Corrected Distance Visual Acuity (CDVA) With the Same Refractive Correction

Visual acuity for near (40 centimeter [cm]) and distance (4 meter [m]) targets were measured in mesopic conditions using an eye chart. High contrast corrected distance visual acuity (CDVA) was assessed binocularly (in each eye) using the provided visual acuity charts for distance vision in a room with mesopic lighting conditions (10 to 11 lux) measured at the target. Both near vision and distance vision were measured to evaluate the effect of AGN-190584. A participant who gained 3 lines or more in mesopic, high contrast, binocular DCNVA with no more than 5-letter loss in mesopic CDVA with the same refractive correction was regarded as a responder. A participant with missing data was regarded as a non-responder. (NCT04983589)
Timeframe: 3 hours after second dose on Day 14

Interventionpercentage of participants (Number)
Vehicle7.8
AGN-19058435.1

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Percentage of Participants Gaining 3 Lines or More in Photopic, High-Contrast, Binocular DCNVA With No More Than a 5-Letter Loss in Photopic CDVA With the Same Refractive Correction

Visual acuity for near (40 centimeter [cm]) and distance (4 meter [m]) targets were measured in photopic conditions using an eye chart. High contrast corrected distance visual acuity (CDVA) was assessed binocularly (in each eye) using the provided visual acuity charts for distance vision in a room with photopic lighting conditions (≥ 251 lux) measured at the target. Both near vision and distance vision were measured to evaluate the effect of AGN-190584. A participant who gained 3 lines or more in photopic, high contrast, binocular DCNVA with no more than 5-letter loss in photopic CDVA with the same refractive correction was regarded as a responder. A participant with missing data was regarded as a non-responder. (NCT04983589)
Timeframe: 3 hours after second dose on Day 14

Interventionpercentage of participants (Number)
Vehicle6.0
AGN-19058432.5

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Number of Participants With Constricting Response to Pilocarpine 1% in the Pharmacologically Dilated Eye

Measurement of pupil diameter (NCT05238233)
Timeframe: 4 hours

InterventionParticipants (Count of Participants)
Eye Dilation and Constriction3

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