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hexamethonium

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Description

Hexamethonium is a quaternary ammonium compound that acts as a ganglion blocker. It was synthesized in the 1940s and was initially used to treat hypertension. Hexamethonium blocks the transmission of nerve impulses at autonomic ganglia, resulting in a decrease in blood pressure. It has also been studied for its effects on other physiological processes, including bladder control and muscle tone. Hexamethonium is no longer widely used clinically due to its significant side effects, including postural hypotension and constipation. It is still used in research to investigate the role of the autonomic nervous system in various physiological processes.'

Hexamethonium: A nicotinic cholinergic antagonist often referred to as the prototypical ganglionic blocker. It is poorly absorbed from the gastrointestinal tract and does not cross the blood-brain barrier. It has been used for a variety of therapeutic purposes including hypertension but, like the other ganglionic blockers, it has been replaced by more specific drugs for most purposes, although it is widely used a research tool. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID3604
CHEMBL ID100622
CHEMBL ID332524
CHEBI ID5700
SCHEMBL ID34900
MeSH IDM0028070

Synonyms (92)

Synonym
hexamethonum
brn 1760389
esametonio [italian]
hexane-1,6-bis(trimethylammonium)
bistrium
hexonium
benzohexamethonium
ammonium, hexamethylenebis(trimethyl-
1,6-hexanediaminium, n,n,n,n',n',n'-hexamethyl-
bdbm50038416
chembl100622 ,
hexamethoniumdibromide
n,n,n,n'''',n'''',n''''-hexamethyl-1,6-hexanediaminium dibromide
(1,6-trimethyl ammonium)hexane; dibromide
n,n,n,n'''',n'''',n''''-hexamethylhexane-1,6-diammoniumdibromide
KBIO1_000663
DIVK1C_000663
SPECTRUM_001659
NCGC00015496-01
lopac-h-0879
NCGC00015496-02
lopac-h-2138
SPECTRUM5_001213
IDI1_000663
PRESTWICK3_000038
BSPBIO_000135
PRESTWICK2_000038
BSPBIO_002567
LOPAC0_000622
AB00053821
60-26-4
C07510
hexamethonium
BPBIO1_000149
NCGC00163239-01
KBIO2_004707
KBIO2_002139
KBIO3_001787
KBIOGR_001462
KBIOSS_002139
KBIO2_007275
SPBIO_001424
SPECTRUM3_000964
SPBIO_002056
SPECTRUM2_001552
PRESTWICK1_000038
PRESTWICK0_000038
NINDS_000663
SPECTRUM4_001081
LOPAC0_000613
NCGC00162203-01
NCGC00162203-02
NCGC00015496-06
NCGC00015496-05
CHEMBL332524 ,
unii-3c9psp36z2
hexamethonium [inn]
esametonio
3c9psp36z2 ,
cas-60-26-4
n,n,n,n',n',n'-hexamethylhexane-1,6-diaminium
tox21_112036
dtxsid9045053 ,
dtxcid7025053
CCG-204702
NCGC00015496-04
NCGC00015496-03
NCGC00015496-07
hexathonide
hexamethonium ion
chebi:5700 ,
hexamethone
hexamethonium cation
trimethyl[6-(trimethylazaniumyl)hexyl]azanium
gtpl3963
hexamethonium [mi]
hexamethylenebis(trimethylammonium)
n(sup 1),n(sup 1),n(sup 1),n(sup 6),n(sup 6),n(sup 6)-hexamethyl-1,6-hexanediaminium
hexamethonium [who-dd]
.alpha.,.omega.-bis(trimethylammonium)hexane
SCHEMBL34900
NCGC00015496-08
tox21_112036_1
trimethyl-[6-(trimethylammonio)hexyl]ammonium
AB00053821_08
AB00053821_09
DB08960
SBI-0050595.P004
AKOS032954387
Q410557
NCGC00015496-19
NCGC00015496-18

Research Excerpts

Overview

Hexamethonium is a potent anti-hypertensive agent. It is known to be a weak antagonist at the postsynaptic nicotinic acetylcholine receptor.

ExcerptReferenceRelevance
"Hexamethonium is a potent anti-hypertensive agent. "( Use of hexamethonium in arterial hypertension.
RYTAND, DA, 1954
)
2.13
"Hexamethonium is known to be a weak antagonist at the postsynaptic nicotinic acetylcholine receptor but a potent antagonist at the presynaptic nicotinic receptor."( Interaction of decamethonium with hexamethonium or vecuronium in the rat: an isobolographic analysis.
England, AJ; Feldman, SA; Redai, I; Richards, KM, 1995
)
1.29

Actions

Hexamethonium did not inhibit PC, and however, TTX abolished all contractile activity. The increase in fluid absorption during SNS was a neurogenic effect on the jejunal segment, as it was eliminated by mesenteric denervation.

ExcerptReferenceRelevance
"Hexamethonium did not inhibit PC, and however, TTX abolished all contractile activity."( Identification of neurogenic intestinal motility patterns in silver perch (Bidyanus bidyanus) that persist over wide temperature ranges.
Dinning, PG; Harris, JO; Jones, BS; Keightley, LJ; Spencer, NJ; Wiklendt, L, 2021
)
1.34
"The hexamethonium-resistant increase in fluid absorption during SNS was a neurogenic effect on the jejunal segment, as it was eliminated by mesenteric denervation and could be reproduced by stimulation of the nerves surrounding the superior mesenteric artery."( Evidence for separate sympathetic regulation of fluid absorption and blood flow in the feline jejunum.
Sjövall, H, 1984
)
0.75

Treatment

Hexamethonium pretreatment suppressed, in a dose-response manner, the increases in blood pressure, heart rate, and rectal temperature in response to PGF2 alpha-icv. In hexameth onium pre-treated rats, however, the nucleus accumbens dopamine levels were time-locked to ethanol levels in the same area after systemic or local ethanol administration.

ExcerptReferenceRelevance
"Hexamethonium pretreatment (i.v.) greatly and significantly attenuated the pressor response to AngII, with no significant effect on heart rate, indicating that the sympathetic system is involved in the cardiovascular effect of AngII in the PVN."( Angiotensin II in the paraventricular nucleus stimulates sympathetic outflow to the cardiovascular system and make vasopressin release in rat.
Khanmoradi, M; Nasimi, A, 2016
)
1.16
"In hexamethonium-treated rats, the blood-pressure-lowering effect of frII was almost abolished."( Medicinal plants in Suriname: hypotensive effect of Gossypium barbadense.
Hasrat, JA; Pieters, L; Vlietinck, AJ, 2004
)
0.84
"In hexamethonium pre-treated rats, however, the nucleus accumbens dopamine levels were time-locked to the ethanol levels in the same area after systemic or local ethanol administration."( Ethanol-induced dopamine elevation in the rat--modulatory effects by subchronic treatment with nicotinic drugs.
Chau, PP; Löf, E; Söderpalm, B; Stomberg, R, 2007
)
0.85
"Hexamethonium pretreatment suppressed, in a dose-response manner, the increases in blood pressure, heart rate, and rectal temperature in response to PGF2 alpha-icv."( Mechanisms involved in central cardiovascular effects of prostaglandin F2 alpha.
Feuerstein, G; Helke, CJ; Jacobowitz, DM; Kopin, IJ; Zerbe, RL, 1982
)
0.99
"Hexamethonium pretreatment induced significantly less QRS widening and QTc lengthening than was seen in group 1 but worsened the bupivacaine effects on bradycardia, atria-His and PR intervals, mean aortic pressure, and first derivative of left ventricular pressure."( Mechanisms of the putative cardioprotective effect of hexamethonium in anesthetized dogs given a large dose of bupivacaine.
Bassoul, B; Bruelle, P; de La Coussaye, JE; Desch, G; Eledjam, JJ; Lefrant, JY; Peray, PA; Sassine, A, 1994
)
1.26
"Hexamethonium pretreatment resulted in a similar pattern of response except for the immediate and brief 5-HT-induced triad of apnea, bradycardia, and hypotension, which was suppressed."( Parasympathetic component of 5-hydroxytryptamine-induced pulmonary dysfunctions in healthy calves.
Amory, H; Desmecht, DJ; Lekeux, PM; Linden, AS, 1996
)
1.02
"In hexamethonium- or atropine-treated rats, senktide (10 nmol/kg) transiently and selectively enhanced the amplitude of contractions."( In vivo evidence for the involvement of tachykinin NK3 receptors in the hexamethonium-resistant inhibitory transmission in the rat colon.
De Giorgio, R; Giuliani, S; Lecci, A; Maggi, CA; Meini, S; Tramontana, M, 1996
)
1.04
"In hexamethonium-pretreated animals, an atropine-sensitive component of [betaAla(8)]NKA(4-10)-induced colonic contractions was also evident."( Tachykinin NK(2) receptors and enhancement of cholinergic transmission in the inflamed rat colon: an in vivo motility study.
Carini, F; Giuliani, S; Lecci, A; Maggi, CA; Tramontana, M, 2001
)
0.82
"In hexamethonium-treated animals, MEN 10,376 still abolished the increase in insufflation pressure induced by [beta-Ala8]NKA-(4-10) and reduced the increase elicited by capsaicin."( Effects of selective tachykinin receptor antagonists on capsaicin- and tachykinin-induced bronchospasm in anaesthetized guinea-pigs.
Ballati, L; Evangelista, S; Maggi, CA; Manzini, S, 1992
)
0.8
"hexamethonium (2 mg/kg) pretreatment did not abolish the increase in the heart rate, but it delayed the blood pressure increase."( Yohimbine-precipitated clonidine withdrawal: an experimental model of the antihypertensive drug withdrawal syndrome.
Jhamandas, K; Penning, DH, 1992
)
1
"Hexamethonium pretreatment (n = 9) completely abolished all three responses."( Effect and mechanism of vagal nerve stimulation on somatostatin secretion in dogs.
Ahrén, B; Paquette, TL; Taborsky, GJ, 1986
)
0.99
"Pre-treatment with hexamethonium abolished the effects of clonidine on luminal alkalinisation and net fluid flux."( Effects of α2-adrenoceptor stimulation on luminal alkalinisation and net fluid flux in rat duodenum.
Dahlgren, D; Nylander, O; Sedin, J; Sjöblom, M, 2022
)
1.04
"Pretreatment with hexamethonium, a ganglion blocker (20 mg/kg, i.p.), significantly abolished the cardioprotective effects of both early and late phases of RIPC and adenosine preconditioning."( Late Phases of Cardioprotection During Remote Ischemic Preconditioning and Adenosine Preconditioning Involve Activation of Neurogenic Pathway.
Jaggi, AS; Kumar, M; Singh, H; Singh, N, 2019
)
0.84
"Pretreatment with hexamethonium blocked choline's effects on serum lipids and hepatorenal injury markers."( Choline or CDP-choline alters serum lipid responses to endotoxin in dogs and rats: involvement of the peripheral nicotinic acetylcholine receptors.
Cansev, M; Ilcol, YO; Ulus, IH; Yilmaz, Z, 2009
)
0.68
"Pretreatment with hexamethonium bromide, a ganglionic transmission blocker, suppressed the HDR-induced drop of ABP, suggesting that the ABP drop was induced by an inhibition of autonomic neural outflows."( Vestibular control of arterial blood pressure during head-down postural change in anesthetized rabbits.
Hosogai, M; Kawai, Y; Matsuo, S; Nakamura, Y, 2009
)
0.68
"Pretreatment with hexamethonium suppressed the cardiovascular response prior to retching and prolonged the latency to the first retching."( Role of the autonomic nervous system in emetic and cardiovascular responses in Suncus murinus.
Ebukuro, S; Ishii, K; Kuwahara, M; Tsubone, H; Uchino, M, 2002
)
0.64
"Pretreatment with hexamethonium, as well as truncal vagotomy, abolished the gastric motor responses to hyperglycemia (250 mg/dl), and perivagal and gastroduodenal applications of capsaicin significantly reduced the gastric responses to hyperglycemia."( Gastric relaxation induced by hyperglycemia is mediated by vagal afferent pathways in the rat.
Lu, YX; Owyang, C; Zhou, SY, 2008
)
0.67
"Pretreatment with hexamethonium or propranolol produced a marked decrease in cardiac output (CO), although pretreatment with phenoxybenzamine inhibited the decrease in CO during i.v."( Influence of alpha- and beta-adrenergic blockade on systemic and pulmonary hemodynamics during intravenous administration of local anesthetics.
Fujimori, M; Nishimura, K; Tatekawa, S; Yukioka, H, 1984
)
0.59
"Pre-treatment with hexamethonium completely abolished the rise in plasma neuropeptide Y concentrations."( Release of neuropeptide Y in response to splanchnic nerve stimulation in the conscious calf.
Allen, JM; Bircham, PM; Bloom, SR; Edwards, AV, 1984
)
0.59
"Pretreatment with hexamethonium (10 mg/kg) markedly reduced gastric motor response to secretin (5.6 pmol.kg-1.h-1)."( Secretin at physiological doses inhibits gastric motility via a vagal afferent pathway.
Lu, Y; Owyang, C, 1995
)
0.61
"When treatment with hexamethonium bromide or tetrodotoxin into the SAP Stim locus abolished the decreases in atrial rate evoked by SAP and CV Stim, each treatment abolished the decrease in a wave pressure response to SAP Stim but only slightly attenuated the pressure response to CV Stim."( Parasympathetic control of right atrial pressure in anesthetized dogs.
Chiba, S; Furukawa, Y; Inoue, Y; Nakano, H; Oguchi, T; Sawaki, S, 1994
)
0.6
"Pretreatment with hexamethonium reduced 5-HT, 5-MeOT, and ICS 205-930 induced peak increases in SCC by 33, 50, and 36%, respectively."( ICS 205-930 reduces 5-methoxytryptamine-induced short-circuit current in stripped pig jejunum.
Hansen, MB, 1994
)
0.61
"Treatment with hexamethonium abolished the difference in RAP during acute volume infusion."( Preoptic recess lesions reduce right atrial pressure responses to volume expansion.
Bealer, SL, 1996
)
0.63
"Pretreatment with hexamethonium (10 mg/kg iv) significantly reduced the first-phase bronchoconstriction but did not have any measurable effect on the second-phase response."( Cigarette smoke-induced bronchoconstriction: causative agents and role of thromboxane receptors.
Hong, JL; Lee, LY, 1996
)
0.62
"Treatment with hexamethonium reduced nictitating membrane responses at all frequencies of stimulation (by about 75% at 16-32 Hz)."( Assessment of muscarinic transmission in the superior cervical and ciliary ganglion of the cat.
Koss, MC; Rieger, JA, 1997
)
0.64
"Pretreatment with hexamethonium (an autonomic ganglion blocker) greatly attenuated the secretory response, even at a low dose (1 mg/kg given intravenously), although at this dose, the vasodilator response was only slightly affected."( Correlation between vasodilatation and secretion in the lacrimal gland elicited by stimulation of the cornea and facial nerve root of the cat.
Izumi, H; Karita, K; Tamai, M; Yasui, T, 1997
)
0.62
"Pretreatment with hexamethonium (2 mg/kg i.p.), a peripheral blocker of nicotinic receptors, diminished to a similar extent the nicotine-induced ACTH and corticosterone responses."( Effect of indomethacin on nicotine-induced ACTH and corticosterone response.
Borycz, J; Bugajski, J; Gadek-Michalska, A; Głód, R, 1998
)
0.62
"Treatment with hexamethonium before smoking reversed the effect of the smoke on the colitis, improving all parameters."( Cigarette smoke aggravates experimental colitis in rats.
Blennerhassett, PA; Collins, SM; Galeazzi, F; O'Byrne, PM; Qiu, B, 1999
)
0.64
"Pretreatment with hexamethonium could abolish this protection (IA/AR, 67 +/- 4%)."( Bradykinin mediates cardiac preconditioning at a distance.
Schoemaker, RG; van Heijningen, CL, 2000
)
0.63
"Pretreatment with hexamethonium (low toxin concentration; acute denervation) attenuated the effect of toxin A on morphology, luminal MPO activity, and number of RBCs."( Involvement of nerves and calcium channels in the intestinal response to Clostridium difficile toxin A: an experimental study in rats in vivo.
Jodal, M; Lundgren, O; Sörensson, J, 2001
)
0.63
"Treatment with hexamethonium (10 mg/kg, i.v.) prevented the efferent response, but augmented the afferent response."( Inhibitory effects of beta-alanine on the vagal efferent and afferent excitatory responses of the stomach to stimulation of vagal trunk in cats.
Aoki, S; Iwamoto, M; Jino, H; Kawaguchi, A; Kurahashi, K; Oikawa, H, 1992
)
0.62
"Pretreatment with hexamethonium prevented neither acute nor more enduring behavioral deficits observed after TBI."( Blockade of acute hypertensive response does not prevent changes in behavior or in CSF acetylcholine (ACH) content following traumatic brain injury (TBI).
Enters, EK; Kapasi, MZ; McDowell, KP; Pascua, JR; Povlishock, JT; Robinson, SE, 1992
)
0.61
"Pretreatment with hexamethonium reduced the increase in blood flow elicited by electrical stimulation of the facial and glossopharyngeal nerves, but had no effect on that elicited by stimulation of the trigeminal nerve."( Vasodilator responses following intracranial stimulation of the trigeminal, facial and glossopharyngeal nerves in the cat gingiva.
Izumi, H; Karita, K, 1991
)
0.6
"Pretreatment with hexamethonium (1.5 mg/100 g body wt, iv, 2 min before) inhibited plasma glucose, epinephrine and norepinephrine responses to DN1417 (3 nmol/rat, icv)."( Central effects of DN1417, a novel TRH analog, on plasma glucose and catecholamines in conscious rats.
Imura, H; Kabayama, Y; Kato, Y; Ohta, H; Shimatsu, A; Tojo, K, 1985
)
0.59
"Pretreatment with hexamethonium aerosol (3-5 breaths, 10% concentration) completely abolished these immediate changes in breathing patterns, but did not significantly reduce the delayed hyperpnea induced by smoke inhalation."( Hexamethonium aerosol prevents pulmonary reflexes induced by cigarette smoke in dogs.
Lee, LY; Morton, RF, 1986
)
2.04

Toxicity

ExcerptReferenceRelevance
" An additive toxic effect of atropine was suggested with its combinations with TMB4, mecamylamine, and diazepam, whereas no additive toxicity occurred with combinations involving hexamethonium or benactyzine (i."( Efficacy and toxicity of drug combinations in treatment of physostigmine toxicosis.
Klemm, WR, 1983
)
0.46

Compound-Compound Interactions

ExcerptReferenceRelevance
" By using a large photodiode array in combination with a voltage-sensitive dye, membrane potential changes in a slice of the rat adrenal gland were recorded upon brief local electrical stimulation."( Synaptic activation of rat adrenal medulla examined with a large photodiode array in combination with a voltage-sensitive dye.
Iijima, T; Kidokoro, Y; Matsumoto, G, 1992
)
0.28
"Atropine, in combination with 1 of 6 other drugs, was tested in mice for the ability to prevent death by an otherwise lethal dose of the cholinesterase inhibitor, physostigmine."( Efficacy and toxicity of drug combinations in treatment of physostigmine toxicosis.
Klemm, WR, 1983
)
0.27

Bioavailability

ExcerptReferenceRelevance
"Soluble guanylate cyclase (sGC) is the receptor for nitric oxide (NO) and in pathophysiologic conditions where NO formation or bioavailability is impaired, erectile dysfunction (ED) occurs."( Analysis of erectile responses to BAY 41-8543 and muscarinic receptor stimulation in the rat.
Allain, AV; Dhaliwal, JS; Kadowitz, PJ; Lasker, GF; Murthy, SN; Pankey, EA; Stasch, JP, 2013
)
0.39
"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

Dosage Studied

Dose-response curves of vascular resistance changes to intravenous injection of 5-HT were not significantly affected by WAY100635 (5-HT1A antagonist) or GR127935. nicotine dose-response curve was seen in normal rats after blocking peripheral nicotinic receptors by hexamethonium or after bilateral denervation of the adrenal medulla.

ExcerptRelevanceReference
" Dose-response curves to acetylcholine (ACh) and nicotine were established for pairs of tissues with and without epithelium, each pair receiving only one dose of nicotine."( Nicotine-induced airway smooth muscle contraction: neural mechanisms involving the airway epithelium. Functional and histologic studies in vitro.
Bleicher, S; Hahn, HL; Lang, M; Rausch, C; Zwerenz, S,
)
0.13
" This study examines the dose-response effects of rat alpha CGRP on mean circulatory filling pressure (MCFP), an index of body venous tone, in conscious rats."( Calcitonin gene-related peptide is a venous dilator in conscious rats.
Abdelrahman, A; Pang, CC, 1992
)
0.28
"Regional blood volumes (Vb), unstressed volumes (V0), blood flow distribution, venous compliances (Cv), venous resistances (Rv), and time constants of drainage (tau v) were determined in dogs anesthetized with alpha-chloralose at carotid sinus pressures (Pcs) of 50 and 200 mmHg and dosed with alpha-adrenergic or ganglionic blockade at a Pcs of 50 mmHg."( Baroreflex control of regional capacitance and blood flow distribution with or without alpha-adrenergic blockade.
Deschamps, A; Magder, S, 1992
)
0.28
"001) of the mean dose-response relationship."( Cholinergic mechanisms involved with histamine hyperreactivity in immune rabbit airways challenged with ragweed antigen.
Ando, RE; Irvin, CG; Larsen, GL; Tanaka, DT, 1991
)
0.28
" Atropine sulphate administered locally into the skin antagonised the response to carbachol: the dose-response curve for carbachol was shifted to the right without any depression of the maximum of the curve."( Effects of locally and systemically administered cholinoceptor antagonists on the secretory response of human eccrine sweat glands to carbachol.
Bradshaw, CM; Longmore, J; Szabadi, E, 1985
)
0.27
" We investigated whether the maximal response plateau or the position of the dose-response curve is due to functional inhibition by neurogenic mechanisms or to prostaglandin release."( Limited maximal airway narrowing in nonasthmatic subjects. Role of neural control and prostaglandin release.
Daniel, EE; Hargreave, FE; Sterk, PJ; Zamel, N, 1985
)
0.27
" However, the dose-response curves for milrinone were shifted dextrally for changes in +dP/dt and LVEDP, whereas the dose-response curve for blood pressure was shifted sinistrally."( Participation of the autonomic nervous system in the cardiovascular effects of milrinone.
Gorczynski, RJ; Shaffer, JE; Vuong, A, 1986
)
0.27
" The latter interventions, when imposed between successive dose-response curves generated by intravenous 5HT in animals pretreated with atropine and propranolol, did not alter the positions or slopes of the curves."( Reflex activation of the nonadrenergic noncholinergic inhibitory nervous system in feline airways.
Altiere, RJ; Diamond, L; Gillespie, MN; Szarek, JL, 1986
)
0.27
"The dose-response curves of the central and peripheral airways to intravenously injected nicotine were studied in 55 anesthetized dogs."( Dose-response curves of central and peripheral airways to nicotine injections in dogs.
Haga, T; Miyano, M; Nakamura, M; Sasaki, H; Takishima, T, 1986
)
0.27
" A method that avoided tachyphylaxis encountered in prior investigations was developed for isometric measurement of multiple dose-response effects."( Parasympathetic involvement in PAF-induced contraction in canine trachealis in vivo.
Leff, AR; Munoz, NM; Popovich, KJ; Shioya, T; Stimler-Gerard, NP; White, SR, 1987
)
0.27
" To determine the time after administration of nicotine and dosage for neurochemical studies, locomotor activity of CD-1 mice was determined at 5 min intervals between 0-60 min."( Locomotor activity as a predictor of times and dosages for studies of nicotine's neurochemical actions.
Freeman, GB; Gibson, GE; Sherman, KA, 1987
)
0.27
" Dose-response curves were constructed for the increase in cGMP-immunofluorescence intensity for K+ and carbachol."( Single cell quantitative immunocytochemistry of cyclic GMP in the superior cervical ganglion of the rat.
Garssen, J; Schipper, J; Steinbusch, HW; Tilders, FJ; Vente, JD, 1987
)
0.27
" Dose-response curves to acetylcholine (n = 8) and histamine (n = 4) were measured before and after exposure to ozone (3 ppm for 30 min)."( Role of the parasympathetic nervous system in airway hyperresponsiveness after ozone inhalation.
Jones, GL; Lane, CG; Manning, PJ; O'Byrne, PM, 1987
)
0.27
" Hexamethonium pretreatment suppressed, in a dose-response manner, the increases in blood pressure, heart rate, and rectal temperature in response to PGF2 alpha-icv."( Mechanisms involved in central cardiovascular effects of prostaglandin F2 alpha.
Feuerstein, G; Helke, CJ; Jacobowitz, DM; Kopin, IJ; Zerbe, RL, 1982
)
1.17
" GB converted the negative chronotropic effect to positive chronotropic action but had no effect on the inotropic dose-response relation."( Cardiovascular pharmacology of ASL-7022. II. Mechanisms of inotropic selectivity.
Gorczynski, RJ; Wroble, RW, 1982
)
0.26
" Blocking the direct actions of histamine with concentrations of pyrilamine greater than 10(-7) M resulted in a biphasic histamine dose-response curve: lower histamine concentrations produced a dose-dependent decrease of the twitch response; higher concentrations produced a potentiation."( Histamine receptors in the myenteric plexus-longitudinal muscle of the guinea-pig ileum: H1- and H2-receptor-mediated potentiation of the contractile response to electrical stimulation.
Yellin, TO; Zavecz, JH, 1982
)
0.26
" Cumulative dose-response curves to noradrenaline and methoxamine on the circular contraction of isolated iliac arteries showed a significant shift to the right, together with a reduction in the maximal contraction."( Vascular reactivity in perinatally undernourished rats.
Del Basso, P; Keller, EA; Orsingher, OA; Salica, C, 1983
)
0.27
" Trimethaphan (10(-4)-10(-3)M) shifted the dose-response curve for norepinephrine in mesenteric arteries to the right, but failed to influence the contractile response to 25 mM KCl."( Trimethaphan is a direct arterial vasodilator and an alpha-adrenoceptor antagonist.
Harioka, T; Hatano, Y; Mori, K; Toda, N, 1984
)
0.27
" Thus, the dose-response curve shows an U-shaped form."( The impairment of retention induced by beta-endorphin in mice may be mediated by a reduction of central cholinergic activity.
Baratti, CM; Introini, IB, 1984
)
0.27
" At 16 weeks of age more-complete dose-response curves to the alpha 1-agonist methoxamine were also constructed."( Arterial hypertrophy and pressor responsiveness during development of hypertension in spontaneously hypertensive rats.
Lee, RM; Leenen, FH; Tsoporis, J; Yuan, B, 1994
)
0.29
" nicotine dose-response curve was seen in normal rats after blocking peripheral nicotinic receptors by hexamethonium or after bilateral denervation of the adrenal medulla."( Adrenal medullary modulation of the inhibition of bradykinin-induced plasma extravasation by intrathecal nicotine.
Basbaum, AI; Benowitz, NL; Dallman, MF; Levine, JD; Miao, FJ, 1993
)
0.5
" The pancreatic dose-response curve to 40-min venous infusions of neurotensin 1-13 (0."( Mechanism of neurotensin stimulation of external pancreatic secretion in the rat.
Chariot, J; Nagain, C; Rozé, C, 1993
)
0.29
" When stimulated by nicotine or carbachol, the dose-response curves of both cell fractions yielded similar EC50s for the release of adrenaline and noradrenaline."( Catecholamine release from fractionated chromaffin cells.
Krause, W; Livett, BG; Lübke, C; Michael, N; Oehme, P, 1996
)
0.29
" The dose-response relation for IACh versus ACh concentration was fitted by the Hill equation with EC50 = approx."( Nicotinic acetylcholine sensitivity of rat petrosal sensory neurons in dissociated cell culture.
Nurse, CA; Zhong, H, 1997
)
0.3
" At the lowest dose studied (20 microgram/kg iv), the inhibitory effects of candesartan were competitive, whereas at the highest dose (100 microgram/kg iv) the dose-response curve for angiotensin II was shifted to the right in a nonparallel manner with inhibitory effects that could not be surmounted."( Role of AT(1) receptors and autonomic nervous system in mediating acute pressor responses to ANG II in anesthetized mice.
Bivalacqua, TJ; Champion, HC; Dalal, A; Kadowitz, PJ, 1999
)
0.3
"6 microgram/mouse inhibited the acquisition of avoidance conditioning in mice, and kappa-BTX yielded this effect with a dose-response relationship."( Subtypes of central nicotinic receptors involved in learning and memory.
Chen, LJ; Chen, RZ, 1999
)
0.3
" However, inflammation induced a significant leftward shift in the circular muscle inhibitory dose-response curve of M(2) inhibitor."( Inflammation inhibits muscarinic signaling in in vivo canine colonic circular smooth muscle cells.
Jadcherla, SR, 2002
)
0.31
" Both markers co-varied with a similar dose-response and time course after the nicotine-treatment."( Nicotine-induced inflammatory decreasing effect on passive skin arthus reaction in paraventricular nucleus-lesioned wistar rats.
Kita, T; Kubo, K; Nakashima, T; Nakatani, T; Narushima, I; Tanaka, T, 2003
)
0.32
" Nefiracetam potentiated alpha4beta2-like ACh- and NMDA-induced currents at nanomolar concentrations forming bell-shaped dose-response curves with the maximum potentiation occurring at 1 and 10 nM, respectively."( Unique mechanism of action of Alzheimer's drugs on brain nicotinic acetylcholine receptors and NMDA receptors.
Marszalec, W; Moriguchi, S; Narahashi, T; Yeh, JZ; Zhao, X, 2003
)
0.32
" Dose-response curves of vascular resistance changes to intravenous injection of 5-HT were not significantly affected by WAY100635 (5-HT1A antagonist), GR127935 (5-HT(1B/1D) antagonist), methiothepin (5-HT2C and 5-HT7 antagonist), ketanserin (5-HT2A antagonist), SB203186 (5-HT4 antagonist) or cervical sympathectomy, but were blocked by the 5-HT(3/4) antagonist tropisetron, the 5-HT3 antagonist ondansetron, the ganglion-blocking drug hexamethonium and by vagotomy."( Dilatation induced by 5-HT in the middle meningeal artery of the anaesthetised cat.
Boers, PM; Donaldson, C; Hoskin, KL; Lambert, GA; Zagami, AS, 2004
)
0.49
" In the abdominal constriction test, LXM-10 had a significant dose-response effect, and the maximal inhibition ratio was 79."( Antinociceptive effects of the novel spirocyclopiperazinium salt compound LXM-10 in mice.
Li, CL; Li, RT; Sun, Q; Ye, J; Yue, CQ, 2007
)
0.34
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
quaternary ammonium saltDerivatives of ammonium compounds, (NH4(+))Y(-), in which all four of the hydrogens bonded to nitrogen have been replaced with univalent (usually organyl) groups.
[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 (16)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
RAR-related orphan receptor gammaMus musculus (house mouse)Potency26.60320.006038.004119,952.5996AID1159521
NFKB1 protein, partialHomo sapiens (human)Potency1.25890.02827.055915.8489AID895; AID928
GLS proteinHomo sapiens (human)Potency7.94330.35487.935539.8107AID624146
thyroid stimulating hormone receptorHomo sapiens (human)Potency39.81070.001318.074339.8107AID926; AID938
regulator of G-protein signaling 4Homo sapiens (human)Potency0.11920.531815.435837.6858AID504845
glucocorticoid receptor [Homo sapiens]Homo sapiens (human)Potency15.08900.000214.376460.0339AID720691
estrogen nuclear receptor alphaHomo sapiens (human)Potency33.49150.000229.305416,493.5996AID743079
arylsulfatase AHomo sapiens (human)Potency1.51011.069113.955137.9330AID720538
euchromatic histone-lysine N-methyltransferase 2Homo sapiens (human)Potency24.90530.035520.977089.1251AID504332
D(1A) dopamine receptorHomo sapiens (human)Potency0.14580.02245.944922.3872AID488982
atrial natriuretic peptide receptor 1 precursorHomo sapiens (human)Potency37.93300.134610.395030.1313AID1347049
ras-related protein Rab-9AHomo sapiens (human)Potency58.04790.00022.621531.4954AID485297
M-phase phosphoprotein 8Homo sapiens (human)Potency37.68580.177824.735279.4328AID488949
muscarinic acetylcholine receptor M1Rattus norvegicus (Norway rat)Potency0.00890.00106.000935.4813AID943
Spike glycoproteinSevere acute respiratory syndrome-related coronavirusPotency4.46680.009610.525035.4813AID1479145
ATP-dependent phosphofructokinaseTrypanosoma brucei brucei TREU927Potency0.75690.060110.745337.9330AID485368
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Ceullar Components (1)

Processvia Protein(s)Taxonomy
virion membraneSpike glycoproteinSevere acute respiratory syndrome-related coronavirus
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (49)

Assay IDTitleYearJournalArticle
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
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.
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.
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.
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.
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.
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.
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.
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.
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.
AID1745845Primary qHTS for Inhibitors of ATXN expression
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
AID588378qHTS for Inhibitors of ATXN expression: Validation
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.
AID588349qHTS for Inhibitors of ATXN expression: Validation of Cytotoxic Assay
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 (2,188)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990943 (43.10)18.7374
1990's693 (31.67)18.2507
2000's402 (18.37)29.6817
2010's130 (5.94)24.3611
2020's20 (0.91)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 46.56

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 strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index46.56 (24.57)
Research Supply Index7.74 (2.92)
Research Growth Index4.20 (4.65)
Search Engine Demand Index78.00 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (46.56)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials3 (0.13%)5.53%
Reviews6 (0.26%)6.00%
Case Studies17 (0.74%)4.05%
Observational0 (0.00%)0.25%
Other2,261 (98.86%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]