Page last updated: 2024-12-04

dantrolene

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Description

Dantrolene is a skeletal muscle relaxant that acts as a ryanodine receptor antagonist. It is used to treat malignant hyperthermia, a life-threatening condition that can occur during general anesthesia. Dantrolene is also used to treat spasticity, a condition that causes muscles to become stiff and difficult to move. The synthesis of dantrolene involves a multi-step process that starts with a substituted 2-pyridone derivative. Dantrolene is studied for its potential therapeutic applications in various neurological conditions such as spinal cord injury, stroke, and multiple sclerosis. Research is ongoing to further understand its mechanism of action and develop new therapeutic uses for this compound.'

Dantrolene: Skeletal muscle relaxant that acts by interfering with excitation-contraction coupling in the muscle fiber. It is used in spasticity and other neuromuscular abnormalities. Although the mechanism of action is probably not central, dantrolene is usually grouped with the central muscle relaxants. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

dantrolene : The hydrazone resulting from the formal condensation of 5-(4-nitrophenyl)furfural with 1-aminohydantoin. A ryanodine receptor antagonist used for the relief of chronic severe spasticity and malignant hyperthermia. [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 CID6914273
CHEMBL ID1201288
SCHEMBL ID40893
SCHEMBL ID12417164
MeSH IDM0005658
PubMed CID2952
CHEMBL ID1741132
CHEBI ID4317
SCHEMBL ID56848
MeSH IDM0005658

Synonyms (125)

Synonym
BIDD:GT0187
BRD-K81272440-001-02-6
BRD-K81272440-236-05-1
CHEMBL1201288
f-368
BSPBIO_000222
IDI1_033775
PRESTWICK3_000291
1-({(1e)-[5-(4-nitrophenyl)furan-2-yl]methylidene}amino)imidazolidine-2,4-dione
1-(((5-(4-nitrophenyl)-2-furanyl)methylene)amino)-2,4-imidazolidinedione
dantroleno [inn-spanish]
hsdb 3050
brn 0705189
dantrolenum [inn-latin]
2,4-imidazolidinedione, 1-(((5-(4-nitrophenyl)-2-furanyl)methylene)amino)-
hydantoin, 1-((5-(p-nitrophenyl)furfurylidene)amino)-
einecs 230-684-8
LOPAC0_000424
BSPBIO_001305
SPECTRUM5_001752
BSPBIO_003074
BCBCMAP01_000067
PRESTWICK2_000291
IDI1_000898
BPBIO1_000246
C06939
1-((5-(p-nitrophenyl)furfurylidene)amino)hydantoin
DB01219
dantrolene (usan/inn)
D02347
NCGC00163402-01
NCGC00163402-02
HMS1989B07
dantroleno
dantrolenum
1-({[5-(4-nitrophenyl)furan-2-yl]methylidene}amino)imidazolidine-2,4-dione
HMS1361B07
HMS1791B07
NCGC00188950-01
NCGC00163402-03
1-[(e)-[5-(4-nitrophenyl)furan-2-yl]methylideneamino]imidazolidine-2,4-dione
f64qu97qcr ,
dantrolene [usan:inn:ban]
unii-f64qu97qcr
dantrolene [hsdb]
1-(((5-(4-nitrophenyl)-2-furyl)methylene)amino)imidazolidine-2,4-dione
dantrolene [inn]
dantrolene [usp-rs]
dantrolene [vandf]
dantrolene [mi]
dantrolene [who-dd]
dantrolene [usan]
833480-90-3
SCHEMBL40893
SCHEMBL12417164
2,4-imidazolidinedione, 1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-
1-[[5-(p-nitrophenyl)furfurylidene]amino]hydantoin
1-(((e)-[5-(4-nitrophenyl)-2-furyl]methylidene)amino)-2,4-imidazolidinedione #
HMS3402B07
1-[5-(4-nitro-phenyl)-furan-2-ylmethyleneamino]-imidazolidine-2,4-dione
1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidinedione
SR-01000076241-8
bdbm50198767
Z91274084
[4-(5-{(e)-[(2,4-dioxoimidazolidin-1-yl)imino]methyl}furan-2-yl)phenyl](hydroxy)oxoammonium
DTXSID70873546
A13928
EN300-119181
AMY8921
1-(((5-(4-nitrophenyl)furan-2-yl)methylene)amino)imidazolidine-2,4-dione
BS-48947
1-[(e)-{[5-(4-nitrophenyl)furan-2-yl]methylidene}amino]imidazolidine-2,4-dione
EN300-21037765
CS-0011998
HY-12542
dantrolene (usp-rs)
dantrolenum (inn-latin)
hydantoin, 1-((5-(p-nitrophenyl)furfurylidene)amino-
1-(((5-(4-nitrophenyl)furan-2-yl)methylidene)amino)imidazolidine-2,4-dione
dantroleno (inn-spanish)
dtxcid602881
m03ca01
AKOS040759404
CBIOL_001748
DIVK1C_000898
KBIO1_000898
SPECTRUM_001537
BIO1_001012
BIO1_000523
BIO2_000505
BIO1_000034
BIO2_000025
dantrolene
7261-97-4
KBIO2_000025
KBIO3_002574
KBIO2_005161
KBIO2_002593
KBIOGR_000025
KBIO3_000050
KBIO3_000049
KBIOGR_000645
KBIOSS_002017
KBIOSS_000025
KBIO2_004585
KBIO2_002017
KBIO2_007153
PRESTWICK0_000291
SPECTRUM4_000163
SPBIO_001199
SPBIO_002441
SPECTRUM3_001567
NINDS_000898
PRESTWICK1_000291
SPECTRUM2_001180
CHEBI:4317 ,
FT-0603135
SCHEMBL56848
1-[5-(p-nitrophenyl)-furfurylidene]amino hydantoin
CHEMBL1741132
DTXSID7022881 ,
FT-0665467
dantrolenum; dantrium; dantrolenum
BCP33078
HMS3745A21

Research Excerpts

Overview

Dantrolene (DTN) is a ryanodine receptor (RyR) antagonist that inhibits Ca. It is used for the treatment of the rare genetic disorder, malignant hyperthermia (MH)

ExcerptReferenceRelevance
"Dantrolene is a promising new therapeutic agent in the treatment of cerebral vasospasm. "( The Role of Parenteral Dantrolene in the Contemporary Management of Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review.
Nunna, RS; Ortiz, M; Qureshi, AI; Ravipati, K; Siddiq, F; Tran, A, 2022
)
2.47
"Dantrolene is a ryanodine receptor blocker that is used clinically for treatment of malignant hyperthermia. "( Dantrolene reduces platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell proliferation and neointimal formation following vascular injury in mice.
Akase, H; Inamitsu, M; Kobayashi, S; Mikawa, M; Nakamura, Y; Oda, T; Okamura, T; Sakai, C; Suetomi, T; Tominaga, N; Uchida, T; Yamamoto, T; Yano, M, 2022
)
3.61
"Dantrolene (DTN) is a ryanodine receptor (RyR) antagonist that inhibits Ca"( Dantrolene and ryanodine receptors in COVID-19: The daunting task and neglected warden.
Ahmed, EA; Al-Gareeb, AI; Al-Kuraishy, HM; Alkazmi, L; Batiha, GE; El-Bouseary, MM, 2023
)
3.8
"Dantrolene is an intra-cellularly acting skeletal muscle relaxant used for the treatment of the rare genetic disorder, malignant hyperthermia (MH). "( Molecular Aspects Implicated in Dantrolene Selectivity with Respect to Ryanodine Receptor Isoforms.
Gaburjakova, J; Gaburjakova, M, 2023
)
2.64
"Dantrolene is a neutral hydantoin that is clinically used as a skeletal muscle relaxant to prevent overactivation of the skeletal muscle calcium release channel (RyR1) in response to volatile anesthetics. "( Dantrolene inhibition of ryanodine channels (RyR2) in artificial lipid bilayers depends on FKBP12.6.
Beard, N; Laver, DR; van Helden, DF; Walweel, K, 2023
)
3.8
"Dantrolene sodium is a ryanodine receptor antagonist."( Dantrolene Induces Mitigation of Myocardial Ischemia-Reperfusion Injury by Ryanodine Receptor Inhibition.
Dedeilias, P; Deftereos, S; Kotanidou, A; Papakonstantinou, NA; Papalois, A; Samiotis, I; Vasileiadis, I, 2022
)
2.89
"Dantrolene is a ryanodine receptor antagonist and is used as an anti-inflammatory agent."( Beneficial effects of dantrolene in the treatment of rhabdomyolysis as a potential late complication associated with COVID-19: a case report.
Chiba, N; Kinoshita, K; Matsuzaki, M; Mawatari, T; Mizuochi, M; Sakurai, A, 2021
)
1.66
"Dantrolene is a ryanodine receptor (RyR) inhibitor, which is used to relax muscles in malignant hyperthermia syndrome. "( Dantrolene Requires Mg
Almássy, J; Csernoch, L; Diszházi, G; Jóna, I; Magyar, ZÉ; Mótyán, JA; Nánási, PP, 2019
)
3.4
"Dantrolene is a clinically used muscle relaxant that has recently been found to exert antiarrhythmic effects against SR Ca"( The emerging role of calmodulin regulation of RyR2 in controlling heart rhythm, the progression of heart failure and the antiarrhythmic action of dantrolene.
Laver, DR; Oo, YW; Walweel, K, 2017
)
1.38
"Dantrolene sodium (Da) is an effective skeletal muscle relaxant. "( Preparation, characterization and in vivo evaluation of a formulation of dantrolene sodium with hydroxypropyl-β-cyclodextrin.
Chen, M; Jiang, J; Jin, X; Liu, S; Wang, M; Wu, Q; Zhao, C, 2017
)
2.13
"Dantrolene is a skeletal muscle relaxant used commonly in performance horses to prevent exertional rhabdomyolysis. "( Pharmacokinetics and metabolism of dantrolene in horses.
Arthur, RM; DiMaio Knych, HK; Moeller, BC; Stanley, SD; Taylor, A, 2011
)
2.09
"Dantrolene sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered."( Malignant hyperthermia in the oral and maxillofacial surgery patient: an update.
Patil, PM, 2011
)
1.09
"Dantrolene (1) is a substrate for breast cancer resistant protein, which is widely distributed in the blood-brain-barrier, intestine, gall bladder, and liver. "( Radiosynthesis of [13N]dantrolene, a positron emission tomography probe for breast cancer resistant protein, using no-carrier-added [13N]ammonia.
Fujinaga, M; Fukumura, T; Kumata, K; Nengaki, N; Ogawa, M; Suzuki, K; Takei, M; Yoshida, Y; Zhang, MR, 2012
)
2.13
"Dantrolene is a drug that suppresses intracellular Ca(2+) release from sarcoplasmic reticulum (SR) in skeletal muscle and is used as a therapeutic agent in individuals susceptible to malignant hyperthermia. "( Identification of a dantrolene-binding sequence on the skeletal muscle ryanodine receptor.
Bhat, MB; Ikemoto, N; Jimenez, LS; Ma, J; Morimoto, H; Parness, J; Paul-Pletzer, K; Williams, PG; Yamamoto, T, 2002
)
2.08
"Dantrolene is a skeletal muscle relaxant that depresses the excitation-contraction coupling,however, the specificity of action remains unknown."( [Dantrolene. Pharmacological and therapeutic aspects].
Agarwal, K; Fiege, M; Gerbershagen, MU; Krause, T; Wappler, F, 2003
)
1.95
"Dantrolene is an inhibitor of a skeletal muscle subtype of ryanodine receptors that stabilizes intracellular calcium concentrations and exerts neuroprotective effects in neurons submitted to excitotoxic challenges. "( Dantrolene inhibits NMDA-induced 45Ca uptake in cultured cerebellar granule neurons.
Makarewicz, D; Ziemińska, E; Łazarewicz, JW,
)
3.02
"Dantrolene is an inhibitor of intracellular Ca2+ release from skeletal muscle SR (sarcoplasmic reticulum). "( Probing a putative dantrolene-binding site on the cardiac ryanodine receptor.
Ikemoto, N; Jimenez, LS; Ma, J; Morimoto, H; Parness, J; Paul-Pletzer, K; Williams, PG; Yamamoto, T, 2005
)
2.1
"Dantrolene is a ryanodine receptor and intracellular calcium antagonist. "( Ryanodine receptor antagonism protects the ischemic liver and modulates TNF-alpha and IL-10.
López-Neblina, F; Toledo, AH; Toledo-Pereyra, LH; Walsh, J, 2007
)
1.78
"Dantrolene is a directly acting muscle relaxant which lowers the body temperature in malignant hyperthermia."( Use of dantrolene in experimental scorpion envenomation by Androctonus australis hector.
Bechis, G; Devaux, C; Guieu, R; Kopeyan, C; Rochat, H; Sampieri, F, 1995
)
1.47
"Dantrolene sodium (DS) is a direct-acting skeletal muscle relaxant whose only known action is to block calcium release from intracellular storage sites. "( Dantrolene sodium can increase or attenuate activity of skeletal muscle ryanodine receptor calcium release channel. Clinical implications.
Lin, M; Nelson, TE; Sudo, RT; Zapata-Sudo, G, 1996
)
3.18
"Dantrolene is an agent that interferes with intracellular calcium fluxes resulting in a decreased availability of calcium in the cytoplasm."( Modulation by dantrolene of endotoxin-induced interleukin-10, tumour necrosis factor-alpha and nitric oxide production in vivo and in vitro.
Haskó, G; Lendvai, B; Németh, ZH; Szabó, C; Vizi, ES, 1998
)
1.38
"Dantrolene sodium is a medically important hydantoin derivative that interferes with release of Ca2+ from intracellular stores of skeletal muscle by an unknown mechanism. "( [3H]Azidodantrolene: synthesis and use in identification of a putative skeletal muscle dantrolene binding site in sarcoplasmic reticulum.
Bin, B; Jimenez, LS; Morimoto, H; Palnitkar, SS; Parness, J; Paul-Pletzer, K; Williams, PG, 1999
)
2.16
"Dantrolene sodium is a clinically used drug that modulates myocardial [Ca2+]i handling in animal models."( Dantrolene sodium improves the force-frequency relationship and beta-adregenic responsiveness in failing human myocardium.
Haake, N; Hirt, S; Meissner, A; Min, JY; Simon, R, 1999
)
2.47
"Dantrolene (Dantrium) is a muscle relaxing agent used for the treatment of spastic neurological manifestations which has known liver toxicity."( [Dantrolene-induced pleurisy: a case report].
Dohen, F; Lelieur, E; Montagne, V, 2000
)
1.94
"Dantrolene is a skeletal muscle relaxant which acts by inhibiting intracellular Ca(2+) release from sarcoplasmic reticulum (SR). "( The skeletal muscle ryanodine receptor identified as a molecular target of [3H]azidodantrolene by photoaffinity labeling.
Jimenez, LS; Morimoto, H; Palnitkar, SS; Parness, J; Paul-Pletzer, K, 2001
)
1.98
"Dantrolene sodium is a skeletal muscle relaxant, which inhibits intracellular Ca2+ release from the sarcoplasmic reticulum. "( In vitro antioxidant properties of dantrolene sodium.
Büyükokuroğlu, ME; GülçIn, I; Küfrevioğlu, OI; Oktay, M, 2001
)
2.03
"Dantrolene sodium is a muscle relaxant used in the treatment of spasticity. "( The effect of dantrolene sodium on rat skeletal muscle in relation to the plasma concentration.
Meyler, WJ; Mols-Thurkow, I; Sargo, S; Scaf, AH; Wesseling, H, 1979
)
2.06
"Dantrolene sodium is a valuable tool in the management of spasticity due to hemiplegia."( Effect of dantrolene sodium on spasticity associated with hemiplegia.
Ferguson, KL; Steinberg, FU, 1975
)
1.38
"Dantrolene is an expensive drug and justification for its routine use in HS remains to be evaluated."( Is dantrolene effective in heat stroke patients?
Channa, AB; Kadiwal, GH; Saddique, AA; Samarkandi, AH; Seraj, MA; Shaikh, MH, 1990
)
1.62
"Dantrolene sodium is a drug used in the treatment of spasticity and malignant hyperthermia. "( [In vitro electrophysiological effects of sodium dantrolene on isolated preparations of Purkinje fibers and ventricular myocardium of sheep].
Grosgogeat, Y; Lascault, G; Waxman, MB, 1985
)
1.97
"Dantrolene is a direct acting muscle relaxant which should be avoided in patients with pre-existing liver damage."( Spasticity and drug therapy.
Wuis, EW, 1987
)
0.99
"Dantrolene appears to be an effective treatment for phenelzine toxicity manifested by a hypermetabolic state."( Phenelzine toxicity responsive to dantrolene.
Bennetts, M; Kozachuk, WE; Salanga, VD; Verrilli, MR, 1987
)
1.27
"Dantrolene is an effective antagonist of anesthesia-induced malignant hyperthermia due to a poorly understood action on skeletal muscle. "( Dantrolene and mepacrine antagonize the hemolysis of human red blood cells by halothane and bee venom phospholipase A2.
Fletcher, JE; Kistler, P; Michaux, K; Rosenberg, H, 1987
)
3.16

Effects

Dantrolene has a safe side-effect profile and a mechanism of action that makes it attractive as an option for treatment of cerebral vasospasm. It has an important protective effect on hippocampal neurons apoptosis induced by hyperthermia.

Dantrolene has been shown to block the increase in free intracellular calcium ion stimulated by either NMDA or glutamate. It has been used successfully in NMS on the hypothesis that the syndrome is similar to anesthetic-induced malignant hyperthermia.

ExcerptReferenceRelevance
"Dantrolene has a safe side-effect profile and a mechanism of action that makes it attractive as an option for treatment of cerebral vasospasm. "( Intra-Arterial Dantrolene for Refractory Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage.
Jahngir, M; Litofsky, NS; Nattanmai, P; Ortiz Torres, MJ; Qualls, K; Qureshi, AI, 2019
)
2.31
"Dantrolene sodium has an important protective effect on hippocampal neurons apoptosis induced by hyperthermia and may have some applicative value of preventing heat-induced brain injury."( [Mechanism of Ca2+ on the hyperthermia-induced apoptosis of rat hippocampal neurons in vitro].
Chen, GZ; Chen, XH; Li, TL; Luo, BD; Zhao, QP; Zou, F, 2005
)
1.77
"Dantrolene has an inhibitory action against Ca(2+) release from intracellular Ca(2+) stores."( Dantrolene, a calcium-induced calcium release inhibitor, prevents the acquisition of amygdaloid kindling in rats, a model of experimental epilepsy.
Sakai, T; Yoshida, M, 2006
)
2.5
"Dantrolene has a weak effect on both the thermodynamic and NMR parameters of the pure model membrane."( Dantrolene inhibits halothane-induced membrane reorganization. A study using 31P-NMR and differential scanning calorimetry.
Bonnet, M; Dufourc, EJ; Gaillard, S; Renou, JP, 1992
)
2.45
"Dantrolene has shown promise in several animal studies in the treatment of cerebral vasospasm."( The Role of Parenteral Dantrolene in the Contemporary Management of Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review.
Nunna, RS; Ortiz, M; Qureshi, AI; Ravipati, K; Siddiq, F; Tran, A, 2022
)
1.75
"Dantrolene has aroused considerable recent interest as a lead compound for stabilizing calcium release due to overactive cardiac calcium release channels (RyR2) in heart failure."( Dantrolene inhibition of ryanodine channels (RyR2) in artificial lipid bilayers depends on FKBP12.6.
Beard, N; Laver, DR; van Helden, DF; Walweel, K, 2023
)
3.07
"Dantrolene has shown promising results in controlling muscle symptoms in individuals with ERM, however, its use in children remains poorly documented."( Oral Dantrolene Reduces Myalgia and Hyperckemia in a Child with RYR1-Related Exertional Myalgia/Rhabdomyolysis.
Aschoff, CAM; de Lima Silva, EV; de Souza, CFM; Donis, KC; Machado, FRC; Poswar, FO; Saute, JAM; Simão Medeiros, L, 2023
)
2.15
"Dantrolene has been demonstrated to be neuroprotective for multiple neurodegenerative diseases. "( Intranasal administration of dantrolene increased brain concentration and duration.
Eckenhoff, MF; Liang, G; Meng, Q; Shi, Y; Wang, J; Wang, Y; Wei, H; Yu, S, 2020
)
2.29
"Dantrolene has been shown to stabilize the cardiac ryanodine-receptor."( Dantrolene reduces CaMKIIδC-mediated atrial arrhythmias.
Dybkova, N; Keyser, A; Lebek, S; Maier, LS; Mustroph, J; Neef, S; Pabel, S; Rupprecht, L; Sossalla, S; Stehle, T; Wagner, S, 2020
)
2.72
"Dantrolene has a safe side-effect profile and a mechanism of action that makes it attractive as an option for treatment of cerebral vasospasm. "( Intra-Arterial Dantrolene for Refractory Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage.
Jahngir, M; Litofsky, NS; Nattanmai, P; Ortiz Torres, MJ; Qualls, K; Qureshi, AI, 2019
)
2.31
"Dantrolene has synergistic effects with nimodipine against 5-HT-induced vasoconstriction in isolated cerebral arteries. "( Inhibition of cerebral vasoconstriction by dantrolene and nimodipine.
Moskowitz, MA; Salomone, S; Sims, JR; Soydan, G, 2009
)
2.06
"Dantrolene has been investigated widely for its possible cytoprotective effects against cell damage in different tissue culture or animal models of diseases involving cytotoxicity induced by disruption of intracellular calcium homeostasis in pathogenesis."( The cytoprotective effects of dantrolene: a ryanodine receptor antagonist.
Inan, S; Wei, H, 2010
)
1.37
"Dantrolene has been shown to be neuroprotective by reducing neuronal apoptosis after brain injury in several animal models of neurological disorders. "( Effects of dantrolene on apoptosis and immunohistochemical expression of NeuN in the spinal cord after traumatic injury in rats.
Bertagnolli, AC; Caldeira, FM; de Marco Viott, A; de Melo, EG; de Oliveira, KM; Fukushima, FB; Gomes, MG; Gomes, MV; Serakides, R; Torres, BB, 2010
)
2.19
"Dantrolene has been shown to be neuroprotective by reducing neuronal apoptosis after SCI."( The ameliorating effect of dantrolene on the morphology of urinary bladder in spinal cord injured rats.
Caldeira, F; Gomes, M; Melo, E; Serakides, R; Torres, B, 2011
)
1.39
"Dantrolene sodium has an important protective effect on hippocampal neurons apoptosis induced by hyperthermia and may have some applicative value of preventing heat-induced brain injury."( [Mechanism of Ca2+ on the hyperthermia-induced apoptosis of rat hippocampal neurons in vitro].
Chen, GZ; Chen, XH; Li, TL; Luo, BD; Zhao, QP; Zou, F, 2005
)
1.77
"Dantrolene has an inhibitory action against Ca(2+) release from intracellular Ca(2+) stores."( Dantrolene, a calcium-induced calcium release inhibitor, prevents the acquisition of amygdaloid kindling in rats, a model of experimental epilepsy.
Sakai, T; Yoshida, M, 2006
)
2.5
"Dantrolene also has been utilized successfully in NMS on the hypothesis that the syndrome is similar to anesthetic-induced malignant hyperthermia."( Therapy of syndrome malin.
Conner, CS, 1983
)
0.99
"Dantrolene has only a small effect on these responses which are larger in predominantly slow-twitch fibre preparations."( Does the sarcoplasmic reticulum achieve chemiosmotic equilibrium in relaxed muscle?
Jeacocke, R, 1982
)
0.99
"Dantrolene has been shown to block the increase in free intracellular calcium ion stimulated by either NMDA or glutamate."( [Effects of dantrolene on histological and behavioral outcome in rat CA1 hippocampus after global transient cerebral ischemia].
Kamiyama, Y; Shiraishi, M, 1995
)
1.39
"Dantrolene has been known to affect intracellular Ca2+ concentration ([Ca2+]i) by inhibiting Ca2+ release from intracellular stores in cultured neurons. "( Effect of dantrolene on KCl- or NMDA-induced intracellular Ca2+ changes and spontaneous Ca2+ oscillation in cultured rat frontal cortical neurons.
Hayashi, T; Horiguchi, J; Inagaki, M; Kagaya, A; Oyamada, T; Su, TP; Takebayashi, M; Tawara, Y; Yamawaki, S; Yokota, N, 1997
)
2.14
"Dantrolene sodium has been shown to block the release of intracellular calcium in skeletal muscle. "( Dantrolene blocks intracellular calcium release in smooth muscle: competitive antagonism of thromboxane A2.
Ally, AI; Cunnane, SC; Horrobin, DF; Karmali, RA; Karmazyn, M; Manku, MS; Morgan, RO, 1978
)
3.14
"Dantrolene sodium has been given to 45 patients suffering from dyskinetic syndromes: 33 were suffering from spastic syndromes, either secondary to cerebral lesions at birth, or to other cerebral lesions, or to cord lesions; 9 were affected by infantile dystonic syndromes; 1 by dystonia muscolorum deformans and the last 2 patients were suffering from parkinsonism. "( [Clinical study of dantrolene sodium in the treatment of spastic and dystonic syndromes].
Baldassarre, L; Fraioli, B; Guglielmi, G,
)
1.9
"Dantrolene has a weak effect on both the thermodynamic and NMR parameters of the pure model membrane."( Dantrolene inhibits halothane-induced membrane reorganization. A study using 31P-NMR and differential scanning calorimetry.
Bonnet, M; Dufourc, EJ; Gaillard, S; Renou, JP, 1992
)
2.45
"Dantrolene has been recommended for use in horses at risk of developing postanesthetic myopathy."( Prophylactic use of dantrolene associated with prolonged postanesthetic recumbency in a horse.
Boyd, CJ; Dyson, DH; Pascoe, PJ; Valverde, A, 1990
)
1.32
"Dantrolene sodium has been compared with reference antiarrhythmic agents in rodent models of cardiac arrhythmia. "( Effects of dantrolene sodium in rodent models of cardiac arrhythmia.
Brooks, RR; Carpenter, JF; Gregory, CM; Jones, SM, 1989
)
2.11
"Dantrolene has also been used successfully in the treatment of a few cases of heat stroke and the neuroleptic malignant syndrome--both of which have many similarities to malignant hyperthermia."( Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity.
Chaffman, MO; Sorkin, EM; Ward, A, 1986
)
2.44

Actions

Dantrolene was found to inhibit thymol-stimulated calcium efflux from heavy SR vesicles by 44 +/- 10% (n = 3) at 12 microM. Dantrolenes did not cause additional respiratory depression when administered alone or in combination with other drugs routinely used to treat tetanus. The mechanism responsible for its effects is unclear.

ExcerptReferenceRelevance
"Dantrolene did not suppress operant behavioral output at these doses."( Dantrolene diminishes forelimb force-related tremor at doses that do not decrease operant behavior in the rat.
Fowler, SC; Stanford, JA, 2002
)
2.48
"Dantrolene was shown to inhibit the halothane-induced calcium release."( Calcium-induced Ca2+ release from sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia. The effects of halothane and dantrolene.
Gronert, GA; Ohnishi, ST; Taylor, S, 1983
)
1.19
"Dantrolene failed to inhibit the caffeine- and CCh-induced contractions depending on intracellularly stored Ca."( Inhibitory effects of dantrolene on contractile responses in gastric smooth muscle of the rat.
Ito, S; Nakazato, Y; Ohta, T; Satoh, K, 1994
)
1.32
"Dantrolene was found to inhibit thymol-stimulated calcium efflux from heavy SR vesicles by 44 +/- 10% (n = 3) at 12 microM."( Effects of dantrolene on steps of excitation-contraction coupling in mammalian skeletal muscle fibers.
Collet, C; Csernoch, L; Jacquemond, V; Jona, I; Kovács, L; Sárközi, S; Szegedi, C; Szentesi, P, 2001
)
1.42
"With dantrolene, an 80% increase in creatine phosphate (p less than 0.0001) and a significant decrease in lactate (p less than 0.0001) were found."( The effect of haloperidol, spiperone and dantrolene on the concentrations of creatine phosphate, ATP and lactate in brain and skeletal muscle of the rat during halothane anesthesia.
McLoughlin, JV; Wheatley, AM, 1991
)
1
"Dantrolene is felt to inhibit the release of Ca2+ from vesicular stores but only in response to certain stimuli; the mechanism responsible for its effects is unclear. "( Dantrolene-induced inhibition of insulin release. A mechanism independent of effects on calcium fluxes.
Metz, SA, 1988
)
3.16
"The dantrolene sodium did inhibit superoxide production by the hepatic endoplasmic reticulum in fasted rats."( Inhibition of carbon tetrachloride induced hepatotoxicity by dantrolene sodium.
Born, CK; Davidson, CP; Hamrick, ME; Joyave, JL; Steinhauer, LS, 1986
)
0.99
"Dantrolene did not cause additional respiratory depression when administered alone or in combination with other drugs routinely used to treat tetanus."( Efficacy of dantrolene sodium in management of tetanus in children.
Aguilar Bernal, OR; Bender, MA; Lacy, ME, 1986
)
1.37

Treatment

Dantrolene treatment for 11 months significantly reduced both memory deficits and amyloid plaque load in the hippocampus in 13-month-old 3xTg-AD mice. The drug had no significant side effects on mortality, olfaction, motor, or liver functions.

ExcerptReferenceRelevance
"Dantrolene treatment significantly reduced both AF inducibility (2/9 in dantrolene group, P < 0.05) and AF duration."( Stabilizing Cardiac Ryanodine Receptor With Dantrolene Treatment Prevents Binge Alcohol-Enhanced Atrial Fibrillation in Rats.
Cohen, TJ; Greco, LV; Huang, Y; Kobayashi, S; Li, Y; Migirov, A; Ojamaa, K; Stout, R; Udo-Bellner, L; Zhang, Y, 2022
)
1.7
"Dantrolene treatment had no effect on BP levels in SHR (final systolic BP 212 ± 9 mm Hg in vehicle group vs."( Chronic Dantrolene Treatment Does Not Affect Hypertension, but Attenuates Sympathetic Stimulation Enhanced Atrial Fibrillation Inducibility in SHR.
Gerdes, AM; Greco, L; Lee, JS; Li, Y; Migirov, A; Zhang, Y, 2020
)
1.71
"Dantrolene treatment had no significant change in the amyloid burden or synaptic proteins and no significant side effects on mortality, olfaction, motor, or liver functions in 5XFAD mice."( Intranasal Dantrolene as a Disease-Modifying Drug in Alzheimer 5XFAD Mice.
Ben Abou, M; Eckenhoff, MF; Gao, X; Hepner, A; Liang, G; Meng, Q; Shi, Y; Wei, H; Zhang, J; Zhang, L, 2020
)
1.67
"Dantrolene treatment markedly reduced the rise of [Ca(2+)]i levels caused by chronic administration of ISO (P < .05)."( Effects of Dantrolene Treatment on Ventricular Electrophysiology and Arrhythmogenesis in Rats With Chronic β-Adrenergic Receptor Activation.
Huang, CX; Liu, T; Qin, M; Shi, SB, 2015
)
1.53
"Dantrolene treatment partially normalized Ryr expression and its potential regulators, CAMK IV and calmodulin."( Modulating ryanodine receptors with dantrolene attenuates neuronopathic phenotype in Gaucher disease mice.
Blackwood, R; Dasgupta, N; Fleming, S; Grabowski, GA; Inskeep, V; Li, R; Liou, B; Marshall, J; Peng, Y; Quinn, B; Setchell, KD; Sun, Y; Zhang, W, 2016
)
1.43
"The dantrolene treatment group was perfused in the presence of 5 µmol/L dantrolene before ischemia."( [Effect of dantrolene on energy metabolism in rats with myocardial ischemia-reperfusion].
Cao, Y; Guo, YQ; Li, HD; Wang, LY; Yu, GY; Zhang, YJ; Zhao, XL, 2011
)
1.24
"Dantrolene treatment for 11 months significantly reduced both memory deficits and amyloid plaque load in the hippocampus in 13-month-old 3xTg-AD mice."( Dantrolene ameliorates cognitive decline and neuropathology in Alzheimer triple transgenic mice.
Eckenhoff, MF; Inan, S; Joseph, DJ; Liang, G; Meng, Q; Peng, J; Peng, Y; Wei, H; Wu, Z, 2012
)
2.54
"Dantrolene-treated rats with myocardial infarction were placed into two different dosage groups."( Dantrolene: effects on abnormal intracellular Ca(2+) handling and inotropy in postinfarcted rat myocardium.
Feng, X; Malek, S; Meissner, A; Min, JY; Morgan, JP; Simon, R; Wang, J; Wang, JF, 2003
)
2.48
"Dantrolene is used for treatment of life-threatening hyperthermia, yet its thermoregulatory effects are unknown. "( Dantrolene reduces the threshold and gain for shivering.
Bjorksten, A; Doufas, AG; Kabon, B; Kurz, A; Lenhardt, R; Liem, E; Lin, CM; Muneer Shah, Y; Neeru, S; Sessler, DI; Taguchi, A; Wadhwa, A, 2004
)
3.21
"Dantrolene treatment did not appear to affect virus production, suggesting that Ca2+ release from the ER had a role in the CPE caused by these viruses."( Mutations of a residue within the polyproline-rich region of Env alter the replication rate and level of cytopathic effects in chimeric avian retroviral vectors.
Barsov, EV; Chang, KW; Ferris, AL; Hughes, SH, 2005
)
1.05
"Dantrolene treatment had no protective effects against Zn(2+)-induced cell death."( Calcium and reactive oxygen species mediated Zn2+ -induced apoptosis in PC12 cells.
Abe, S; Ishizawa, K; Kanematsu, Y; Kawazoe, K; Minakuchi, K; Ohnishi, H; Tamaki, T; Torii, M; Tsuchiya, K; Yoshizumi, M, 2006
)
1.06
"Dantrolene treatment was sufficient to reduce twitch amplitude by 25%. "( Dantrolene, like fatigue, has a length-dependent effect on submaximal force-length relationships of rat gastrocnemius muscle.
Campbell, JJ; Maclntosh, BR; MacNaughton, MB, 2007
)
3.23
"Dantrolene pre-treatment results in no significant change in the response of normalized MEPP frequency to tetanus at stimulation rates of both 25 and 100 Hz."( The effect of dantrolene on tetanic potentiation of MEPP frequency in EGTA containing salines.
Publicover, SJ, 1982
)
1.35
"Dantrolene pretreatment of rats (100 mg/kg/day for five days) causes a fifty percent decrease in hepatic mixed function oxidase (MFO) system activity and a fifty percent decrease in cytochrome P450 content. "( Interaction of dantrolene with the hepatic mixed function oxidase system.
Born, CK; Francis, FT; Hamrick, ME; Roy, S, 1980
)
2.06
"In dantrolene-treated animals, EEG total power and median frequency increased within 5 min.(ABSTRACT TRUNCATED AT 250 WORDS)"( Improvement of brain electrical activity during treatment of porcine malignant hyperthermia with dantrolene.
Hoffman, WE; Kochs, E; Schulte am Esch, J, 1993
)
1.02
"Dantrolene effectively treats malignant hyperthermia (MH) hut the current form, Dantrium, must be dissolved to a 0.33 mg/mL, pH 9.5 solution. "( Intravenous lecithin-coated microcrystals of dantrolene are effective in the treatment of malignant hyperthermia: an investigation in rats, dogs, and swine.
Bina, S; Boedeker, BH; Haynes, DH; Karan, SM; Lojeski, EW; Muldoon, SM; Wesche, DL, 1996
)
2
"Dantrolene is the treatment of choice and prognosis depends on the early administration of this agent."( [Intraoperative malignant hyperthermia: apropos of a case].
Antakly, MC; Bou-Khalil, M; Cherfane, A; Madi-Jebara, S; Yazbeck, P, 1997
)
1.02
"On dantrolene treatment, the patient became asymptomatic, and the ischemic test was performed without contracture."( Muscle phosphoglycerate mutase deficiency with tubular aggregates: effect of dantrolene.
Clausen, T; Haller, RG; Schmalbruch, H; Vissing, J, 1999
)
1.05
"Dantrolene treatment also produced a disappearance of thick filaments in some FG fibers."( Loss of thick filaments from fast-twitch glucolytic muscle fibers of the pigeon pectoralis after chronic administration of dantrolene sodium.
Hikida, RS; Silverman, H; Staron, RS, 1979
)
1.19
"Treatment with dantrolene in 4L;C* mice starting at postnatal day 5 delayed neurological pathology and prolonged survival."( Modulating ryanodine receptors with dantrolene attenuates neuronopathic phenotype in Gaucher disease mice.
Blackwood, R; Dasgupta, N; Fleming, S; Grabowski, GA; Inskeep, V; Li, R; Liou, B; Marshall, J; Peng, Y; Quinn, B; Setchell, KD; Sun, Y; Zhang, W, 2016
)
1.05
"The treatment with dantrolene restored the dystrophin and calpain levels near control levels."( Dantrolene improves in vitro structural changes induced by serum from Trypanosoma cruzi-infected mice.
Celes, MR; Jelicks, LA; Malvestio, LM; Prado, CM; Tanowitz, HB, 2017
)
2.22
"Pre-treatment with dantrolene (for 7-10 days) significantly inhibited the inducible VT (P<0.01)."( Dantrolene, a therapeutic agent for malignant hyperthermia, inhibits catecholaminergic polymorphic ventricular tachycardia in a RyR2(R2474S/+) knock-in mouse model.
Doi, M; Kobayashi, S; Matsuzaki, M; Oda, T; Okuda, S; Ono, M; Suetomi, T; Susa, T; Tateishi, H; Uchinoumi, H; Xu, X; Yamamoto, T; Yano, M, 2010
)
2.12
"Pre-treatment with dantrolene protected YAC128 MSNs from glutamate excitotoxicty, with an effective concentration of 100 nM and above."( Dantrolene is neuroprotective in Huntington's disease transgenic mouse model.
Bezprozvanny, I; Chen, X; Herndon, E; Lvovskaya, S; Supnet, C; Wu, J, 2011
)
2.13
"Pre-treatment with dantrolene sodium increases antioxidant enzymes activities and decreases formation of MDA, the indicator of lipid peroxidation, in histamine-induced OME."( Effect of dantrolene on lipid peroxidation, lutathione and glutathione-dependent enzyme activities in experimental otitis media with effusion in guinea pigs.
Aktan, B; Buyukokuroglu, ME; Elmastas, M; Taysi, S; Ucuncu, H, 2005
)
1.05
"Treatment with dantrolene sodium combined with a forced alkaline diuresis resulted in a full recovery."( Postoperative neuroleptic malignant syndrome.
Matthews, EE; Shaw, A, 1995
)
0.63
"Pretreatment with dantrolene produced partial but equal inhibition of acetylcholine (Ach) induced as well as ethanol-induced contraction in equieffective doses."( On mechanism of action of ethanol-induced contraction of frog rectus abdominis.
Kela, AK; Mehta, SC; Mehta, VL; Sharma, AK; Srivastava, AK, 1994
)
0.61
"treatment with dantrolene. The pigs in group A, but not in group B showed slightly increased serum levels of creatine kinase (CK) and aspartate aminotransferase (ASAT) at time of necropsy."( The reduction of skeletal muscle lesions after experimental stress in stress-susceptible pigs protected with dantrolene.
Bjurström, S; Carlsten, J; Jönsson, L, 1995
)
0.84
"Pretreatment with dantrolene for 30 min significantly inhibited elevation of cytosolic Ca2+ levels, DNA fragmentation, and GT1-7 cell death induced by thapsigargin in a dose-dependent manner."( Dantrolene is cytoprotective in two models of neuronal cell death.
Perry, DC; Wei, H, 1996
)
2.06
"Pretreatment with dantrolene completely abolished serotonin-induced MH."( Attenuation of serotonin-induced contractures in skeletal muscle from malignant hyperthermia-susceptible patients with dantrolene.
Fiege, M; Köchling, A; Lambrecht, W; Scholz, J; Schulte am Esch, J; von Richthofen, V; Wappler, F, 1997
)
0.83
"Pretreatment with dantrolene significantly delayed the start of contracture development in MHS muscles, whereas in MHN muscles no contractures were observed after dantrolene."( Attenuation of serotonin-induced contractures in skeletal muscle from malignant hyperthermia-susceptible patients with dantrolene.
Fiege, M; Köchling, A; Lambrecht, W; Scholz, J; Schulte am Esch, J; von Richthofen, V; Wappler, F, 1997
)
0.83
"The treatment with dantrolene sodium markedly reversed such increases."( Dantrolene sodium reverses the increase in cAMP response element and TPA responsive element DNA-binding activity in the rabbit brain following haloperidol administration and heat stress.
Asanuma, M; Iwata, E; Kudo, T; Ogawa, N; Takeda, M; Taniguchi, N; Tanii, H; Tsujio, I, 1997
)
2.06
"A treatment with dantrolene lead to complete remission of the neurotoxic syndrome with no signs of neurological or physical deficits. "( Ping-pong gaze in combined intoxication with tranylcypromine, thioridazine, and clomipramine.
Norra, C; Podoll, K; Prueter, C; Sass, H; Schiefer, J,
)
0.47
"Treatment with dantrolene sodium at the dose used, did not prove beneficial to patients with heatstroke."( Ineffectiveness of dantrolene sodium in the treatment of heatstroke.
Bouchama, A; Cafege, A; Devol, EB; el-Assil, K; Labdi, O; Seraj, M, 1991
)
0.96

Toxicity

Oral dantrolene produced no serious adverse effects within the reported dose range, and was well tolerated by most MH-susceptible patients presenting myopathic symptoms. Dantrolne dose-dependently blocked the toxicity of carbon tetrachloride in recipient culture.

ExcerptReferenceRelevance
"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
" To determine if dantrolene is safe to use in sepsis, two studies were performed."( Is dantrolene safe to administer in sepsis? The effect of dantrolene after endotoxin administration in dogs and rats.
Beebe, DS; Belani, KG; Gillingham, K; Komanduri, V; Palahniuk, RJ; Sweeney, MF; Tuohy, SE, 1991
)
1.24
"A 50 mg/kg dose of dantrolene sodium decreased the hepatotoxicity of carbon tetrachloride in fed and fasted rats, as indicated by lower levels of SGPT following a toxic dose of carbon tetrachloride; however, the dantrolene sodium pretreatment did not inhibit the induction of lipid peroxidation by carbon tetrachloride."( Inhibition of carbon tetrachloride induced hepatotoxicity by dantrolene sodium.
Born, CK; Davidson, CP; Hamrick, ME; Joyave, JL; Steinhauer, LS, 1986
)
0.84
" No adverse effect of dantrolene sodium was detected by extensive testing of the fetus and neonate."( Dantrolene in pregnancy: lack of adverse effects on the fetus and newborn infant.
Andrews, J; Britt, B; Gare, D; Shime, J, 1988
)
2.03
" However, dantrolene dose-dependently blocked the toxicity in the recipient culture, suggesting that the release of intracellular stores of calcium is involved in the toxic effect."( Trauma-induced neurotoxicity in rat hippocampal neurons.
Broder, LD; Brooker, RW; Delisle, RK; Mitchell, HL; Yoon, KW, 1996
)
0.7
" The finding that delta-HCH was more toxic than lindane may be correlated to the differences between the isomers with regard to the action on the different Ca2+ pools."( The mechanism for hexachlorocyclohexane-induced cytotoxicity and changes in intracellular Ca2+ homeostasis in cultured cerebellar granule neurons is different for the gamma- and delta-isomers.
Frandsen, A; Pomés, A; Rodríguez-Farré, E; Rosa, R; Sanfeliu, C; Schousboe, A; Suñol, C, 1997
)
0.3
" Individually, hypertonic Na or DAN treatment partially restored the ability to pace toxic hearts."( The effect of hypertonic sodium and dantrolene on propranolol cardiotoxicity.
Kerns, W; Ransom, M; Raymond, R; Tomaszewski, C, 1997
)
0.57
" High ATP levels may postpone the toxic cascade."( Reactive blue prevented caffeine-induced neurotoxicity by an independent mechanism from intracellular calcium currents in cell culture from auditory cortex of rats.
Bakuridze, K; Büyükokuroglu, ME; Düzenli, S; Gepdiremen, A; Halici, Z; Uçüncü, H, 2005
)
0.33
" Three patients in the IV-D versus two in the placebo group had severe adverse events possibly attributable to infusion and reached stop criteria: one IV-D patient developed liver toxicity; two patients in each group developed brain oedema requiring osmotherapy."( Dantrolene for cerebral vasospasm after subarachnoid haemorrhage: a randomised double blind placebo-controlled safety trial.
Barton, B; Carandang, R; Flood, TF; Garland, B; Gounis, MJ; Hall, W; Izzy, S; Kini, N; Muehlschlegel, S; Ouillette, C; van der Bom, IM; Wakhloo, AK; Weaver, JP, 2015
)
1.86
" The stability study indicated that the system was stable for storage and dilution with distilled water, while the safety testing showed that the micelle was safe for intravenous administration with low hemolysis rates and low allergic reaction rates."( A Novel Dantrolene Sodium-Loaded Mixed Micelle Containing a Small Amount of Cremophor EL: Characterization, Stability, Safety and Pharmacokinetics.
Jiang, D; Jin, W; Li, H; Meng, Y; Song, H; Tan, X; Wen, J; Zhang, Y; Zheng, W, 2019
)
0.95
" Our aim was to investigate the occurrence of serious adverse effects and the adherence to oral dantrolene therapy."( Oral Dantrolene for Myopathic Symptoms in Malignant Hyperthermia-Susceptible Patients: A 25-Year Retrospective Cohort Study of Adverse Effects and Tolerability.
Ibarra Moreno, CA; Jungbluth, H; Kraeva, N; Riazi, S; Voermans, NC; Zvaritch, E, 2023
)
1.64
" There were no serious adverse effects reported."( Oral Dantrolene for Myopathic Symptoms in Malignant Hyperthermia-Susceptible Patients: A 25-Year Retrospective Cohort Study of Adverse Effects and Tolerability.
Ibarra Moreno, CA; Jungbluth, H; Kraeva, N; Riazi, S; Voermans, NC; Zvaritch, E, 2023
)
1.42
"We found that oral dantrolene produced no serious adverse effects within the reported dose range, and was well tolerated by most MH-susceptible patients presenting myopathic symptoms."( Oral Dantrolene for Myopathic Symptoms in Malignant Hyperthermia-Susceptible Patients: A 25-Year Retrospective Cohort Study of Adverse Effects and Tolerability.
Ibarra Moreno, CA; Jungbluth, H; Kraeva, N; Riazi, S; Voermans, NC; Zvaritch, E, 2023
)
1.75

Pharmacokinetics

The half-life of 5-hydroxydantrolene was shorter than that of the parent drug as demonstrated by administration of the metabolite. Physiologically based pharmacokinetic (PBPK) models were coupled with biorelevant dissolution and precipitation data to predict PK profiles.

ExcerptReferenceRelevance
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
Lombardo, F; Obach, RS; Waters, NJ, 2008
)
0.35
" The half-life of 5-hydroxydantrolene was shorter than that of the parent drug as demonstrated by administration of the metabolite."( Pharmacokinetics of intravenously administered dantrolene and its 5-hydroxy metabolite in dogs.
Van Der Kleijn, E; Vree, TB; Wuis, EW, 1990
)
0.83
" Thereafter, the concentration of dantrolene decreased slowly with an elimination half-life (mean +/- SD) of 10."( Pharmacokinetics of intravenous dantrolene in children.
Lerman, J; McLeod, ME; Strong, HA, 1989
)
0.84
" For the pharmacokinetic portion of the study, a randomized, balanced 2-way crossover design was employed wherein eight healthy horses received a single oral dose of either capsules or paste followed by a 4 week washout period prior to administration of the second formulation to the same horse."( Pharmacokinetics and metabolism of dantrolene in horses.
Arthur, RM; DiMaio Knych, HK; Moeller, BC; Stanley, SD; Taylor, A, 2011
)
0.65
" Physiologically based pharmacokinetic (PBPK) models were coupled with biorelevant dissolution and precipitation data to predict PK profiles of dantrolene in fasted humans."( An in vitro-in silico-in vivo approach to predicting the oral pharmacokinetic profile of salts of weak acids: case example dantrolene.
Dressman, JB; Kambayashi, A, 2013
)
0.8

Compound-Compound Interactions

ExcerptReferenceRelevance
" The protective effect of dantrolene potentialized in combination with nimodipine at all doses tested."( The effects of dantrolene alone or in combination with nimodipine in glutamate-induced neurotoxicity in cerebellar granular cell cultures of rat pups.
DüzenlI, S; GepdIremen, A; Hacimüftüoğlu, A; Oztaş, S; Süleyman, H, 2001
)
0.96

Bioavailability

The results were likely due to the relatively high bioavailability of oral dantrolene and, possibly, to continued absorption of dantrole in the postoperative period. Food intake might negatively impact d antrolene bioavailability in horses; however, prolonged feed restriction might be detrimental to performance.

ExcerptReferenceRelevance
" Compound 1 at a concentration of 10 mM in the perfusate induced a twofold reduction of the absorption rate compared with the same concentration of 2 in saline."( Intestinal absorption of drugs. I: The influence of taurocholate on the absorption of dantrolene in the small intestine of the rat.
Crommelin, DJ; Poelma, FG; Tukker, JJ, 1989
)
0.5
" These results were likely due to the relatively high bioavailability of oral dantrolene and, possibly, to continued absorption of dantrolene in the postoperative period."( Plasma levels of dantrolene following oral administration in malignant hyperthermia-susceptible patients.
Allen, GC; Cattran, CB; Lalande, M; Peterson, RG, 1988
)
0.84
"5 h, but was incompletely absorbed, with a bioavailability of 39 +/- 10%."( Pharmacokinetics of dantrolene sodium in horses.
Anwer, MS; Clark, M; Court, MH; Dodman, NH; Engelking, LR; Seeler, DC, 1987
)
0.6
" Food intake might negatively impact dantrolene bioavailability in horses; however, prolonged feed restriction might be detrimental to performance."( Effect of feed restriction on plasma dantrolene concentrations in horses.
Firshman, AM; Garrett, RL; McKenzie, EC; Payton, ME; Riehl, JH; Valberg, SJ, 2010
)
0.91
" By contrast, when only the dissolution was considered, the absorption rate was overestimated."( An in vitro-in silico-in vivo approach to predicting the oral pharmacokinetic profile of salts of weak acids: case example dantrolene.
Dressman, JB; Kambayashi, A, 2013
)
0.6
" In order to solve these problems, an inclusion complex using hydroxypropyl-β-cyclodextrin (HP-β-CD) to improve the oral bioavailability of Da was prepared successfully by freeze-drying."( Preparation, characterization and in vivo evaluation of a formulation of dantrolene sodium with hydroxypropyl-β-cyclodextrin.
Chen, M; Jiang, J; Jin, X; Liu, S; Wang, M; Wu, Q; Zhao, C, 2017
)
0.69

Dosage Studied

Dantrolene sodium, given in the dosage noted, is effective in reduction of analgesic requirements after tonsillectomy. The successful treatment is based on an early diagnosis, immediately interruption of triggering agents and intravenous administration.

ExcerptRelevanceReference
" Depending on the intended indication and dosing regimen, PPL can delay or stop development of a compound in the drug discovery process."( Evaluation of a published in silico model and construction of a novel Bayesian model for predicting phospholipidosis inducing potential.
Gehlhaar, D; Greene, N; Johnson, TO; Pelletier, DJ; Tilloy-Ellul, A,
)
0.13
" We proposed a systematic classification scheme using FDA-approved drug labeling to assess the DILI potential of drugs, which yielded a benchmark dataset with 287 drugs representing a wide range of therapeutic categories and daily dosage amounts."( FDA-approved drug labeling for the study of drug-induced liver injury.
Chen, M; Fang, H; Liu, Z; Shi, Q; Tong, W; Vijay, V, 2011
)
0.37
" Modification of the dosage scheme may be advisable."( Pre-anaesthetic administration of dantrolene sodium to a patient at risk from malignant hyperthermia: case report.
Free, CW; Jaimon, MP, 1978
)
0.54
" Daily dosage of 300 mg or more is associated with higher incidenceof hepatotoxic reactions and with the majority (85%) of the fatalities."( Dantrolene-associated hepatic injury. Incidence and character.
Boitnott, JK; Utili, R; Zimmerman, HJ, 1977
)
1.7
" the dose-response curve on rat diaphragm was flatter."( The effects of dantrolene sodium on cardiac and skeletal muscle in rats.
Agoston, S; Meyler, MJ; Wesseling, H, 1976
)
0.61
" The best dosage schedule was individual and ranged from 50 mg to 300 mg a day."( [Clinical study of dantrolene sodium in the treatment of spastic and dystonic syndromes].
Baldassarre, L; Fraioli, B; Guglielmi, G,
)
0.46
" The dosage of dantrolene ranged from 100 mg per day initially to 600 mg per day maximally."( Effect of dantrolene sodium on spasticity associated with hemiplegia.
Ferguson, KL; Steinberg, FU, 1975
)
1.01
" Dantrium produced no alteration in clinical tone, functional outcome, or biochemical tests at the dosage (200 mg per day) used in this study."( Objective assessment of spasticity, strength, and function with early exhibition of dantrolene sodium after cerebrovascular accident: a randomized double-blind study.
Cole, AM; Katrak, PH; McCauley, JC; Poulos, CJ, 1992
)
0.51
"Two of the persisting controversies concerning malignant hyperthermia (MH) are discussed: storing and dosage of dantrolene and preoperative tactics to be followed with patients who are MH-susceptible."( [An attempt to reconcile differences of opinion in the field of malignant hyperthermia].
Eberlein, HJ; Schulte-Sasse, U, 1991
)
0.49
" The dosage of dantrolene should be decreased when used with theophylline."( A serious interaction of dantrolene and theophylline.
Tayeb, OS, 1990
)
0.94
" We suggest the same dosage regimen as is used in the treatment of malignant hyperthermia."( Acute thyroid crisis on induction of anaesthesia.
Bennett, MH; Wainwright, AP, 1989
)
0.28
" We conclude that dantrolene sodium, given in the dosage noted, is effective in reduction of analgesic requirements after tonsillectomy."( Oral dantrolene sodium for tonsillectomy pain: a double-blind study.
Bellens, EE; Brown, AK; Lenis, A; Ruff, T; Salassa, JR; Seaman, SL, 1988
)
1.12
" Dose-response curves comparing 45Ca efflux and insulin secretion suggested that AA also stimulates hormone release by at least one other mechanism in addition to Ca2+ mobilization."( Exogenous arachidonic acid promotes insulin release from intact or permeabilized rat islets by dual mechanisms. Putative activation of Ca2+ mobilization and protein kinase C.
Metz, SA, 1988
)
0.27
" Based upon disposition kinetics of dantrolene in these studies, intravenous and intragastric dosage regimens were determined which would maintain blood dantrolene concentrations within the predicted clinically effective range."( Pharmacokinetics of dantrolene sodium in horses.
Anwer, MS; Clark, M; Court, MH; Dodman, NH; Engelking, LR; Seeler, DC, 1987
)
0.87
" In the second part of the study, dogs received identical dosage sequences, but verapamil preceded dantrolene administration."( Effects of dantrolene and verapamil on atrioventricular conduction and cardiovascular performance in dogs.
Althaus, JS; Durbin, CG; Fisher, NA; Lynch, C; Veselis, RA, 1986
)
0.88
"The effect of dantrolene sodium, using a dosage of 120 mg/day, was investigated in 3 patients suffering from myotonic dystrophy."( Effect of dantrolene sodium in myotonic dystrophy.
Dal-Bianco, P; Mamoli, B; Zeitlhofer, K, 1983
)
1.03
" The results show that the formulation of dantrolene oral suspension provides a convenient and stable dosage form for use in pediatric patients and in those unable to swallow capsules."( Stability of dantrolene oral suspension prepared from capsules.
Fawcett, JP; Stark, G; Tucker, IG; Woods, DJ, 1994
)
0.92
" Five pigs were orally dosed with dantrolene (5 mg/kg), twice, about 24 and 5 h before the stress (group A)."( The reduction of skeletal muscle lesions after experimental stress in stress-susceptible pigs protected with dantrolene.
Bjurström, S; Carlsten, J; Jönsson, L, 1995
)
0.78
" switching to a low-potency or an atypical antipsychotic, lowering the dosage or discontinuing the NL, and adding a drug effective in treating EPS."( Algorithms for the treatment of acute side effects induced by neuroleptics.
Koyama, T; Kusumi, I, 1999
)
0.3
" Interestingly enough, a nonlinear dose-response curve was obtained for SNP-induced neurotoxicity."( Nitric oxide donor sodium nitroprusside induces neurotoxicity in cerebellar granular cell culture in rats by an independent mechanism from L-type or dantrolene-sensitive calcium channels.
Büyükokuroğlu, ME; Gepdiremen, A; Hacimüftüoğlu, A; Süleyman, H, 2002
)
0.51
" The successful treatment is based on an early diagnosis, immediately interruption of triggering agents, intravenous administration of Dantrolene in sufficient dosage and starting of adequate symptomatic treatment."( [Malignant hyperthermia].
Ben Ammar, MS; Bouhajja, B; Haddad, F, 2002
)
0.52
" Dantrolene-treated rats with myocardial infarction were placed into two different dosage groups."( Dantrolene: effects on abnormal intracellular Ca(2+) handling and inotropy in postinfarcted rat myocardium.
Feng, X; Malek, S; Meissner, A; Min, JY; Morgan, JP; Simon, R; Wang, J; Wang, JF, 2003
)
2.67
" Dantrolene, at 5 mg/kg, was useful to obtain significant protective effects, while the protector effect of higher dantrolene dosing level (10 mg/kg) was weak or absent."( Prevention of acute adriamycin cardiotoxicity by dantrolene in rats.
Bakan, E; Buyukavci, M; Büyükokuroğlu, ME; Taysi, S, 2004
)
1.49
" Current dosing recommendations are based on noncompartmental analyses and are largely empiric."( Compartmental pharmacokinetics of dantrolene in adults: do malignant hyperthermia association dosing guidelines work?
Bouillon, T; Kurz, A; Podranski, T; Schumacher, PM; Sessler, DI; Taguchi, A, 2005
)
0.61
" This paper reviews the various therapeutic options available for childhood-onset dystonia, with a specific attention to dosage and side effects of the drugs regarding pediatric population according to the data of the literature."( [Treatment of childhood dystonia].
Bahi-Buisson, N; Doummar, D; Echenne, B; Payet, C; Roubertie, A; Roze, E, 2010
)
0.36
" Additionally, we discuss the use of dantrolene in dinitrophenol poisoning and question whether current Toxbase/UK National Poison Information Service treatment guidelines regarding the indication and dosing of this drug, the only relatively specific treatment in dinitrophenol poisoning presently recommended, could be revised."( 'Fatal 2,4-dinitrophenol poisoning... coming to a hospital near you'.
Narasimhaiah, R; Siegmueller, C, 2010
)
0.63
" The selectivity of the developed methods was investigated by analyzing laboratory prepared mixtures of the drugs and their combined dosage form."( A comparative study of smart spectrophotometric methods for simultaneous determination of a skeletal muscle relaxant and an analgesic in combined dosage form.
Mohamed, D; Salem, H, 2015
)
0.42
" NMS occurs most often during the first week of treatment or after increasing the dosage of the neuroleptic medication."( [Case report: Neuroleptic malignant syndrome and diagnostic difficulties].
Khouri, C; Logerot, S; Mallaret, M; Planès, S; Villier, C, 2016
)
0.43
" With the approval of the health system's pharmacy and therapeutics committee, the new product was added to the formulary as the preferred dosage form of dantrolene, and existing dantrolene product stock was converted to the new formulation."( Implementation of a new dantrolene formulation across a multifacility health system.
Gross, C; Lang, MB; Skledar, S; Zavilla, CM, 2016
)
0.94
" Reported dosing strategies and outcomes have been summarized."( Neuroleptic Malignant Syndrome.
Cook, AM; Pileggi, DJ, 2016
)
0.43
" The agreement of the simulated pharmacokinetics with the observed values confirms the ability of canine biorelevant media to predict oral performance of enhanced dosage forms in dogs."( Forecasting gastrointestinal precipitation and oral pharmacokinetics of dantrolene in dogs using an in vitro precipitation testing coupled with in silico modeling and simulation.
Dressman, JB; Kambayashi, A, 2017
)
0.69
" Rapid administration and adequate dosage of dantrolene is the only known effective pharmacological and causal treatment of an MH crisis."( [Stocks of dantrolene in anesthesia and intensive care units in Germany : Nationwide online survey with 1673 participants].
Heiderich, S; Klingler, W; Pfenninger, E, 2017
)
1.1
" Current dantrolene dosing recommendations are based on actual body weight despite a paucity of literature in obese patients."( Malignant Hyperthermia in a Morbidly Obese Patient Depletes Community Dantrolene Resources: A Case Report.
Gamble, J; Magistris, F, 2017
)
1.11
" The consensus process used a modified web-based Delphi exercise, in which participants rated the appropriateness of statements that covered the dosing regimen for dantrolene in a malignant hyperthermia crisis, the types of facility that should stock dantrolene, and the amount of dantrolene that should be stocked."( Availability of dantrolene for the management of malignant hyperthermia crises: European Malignant Hyperthermia Group guidelines.
Bendixen, D; Girard, T; Glahn, KPE; Hopkins, PM; Johannsen, S; Rüffert, H; Snoeck, MM; Urwyler, A, 2020
)
1.1
" The powdered drug can alter the specified dosage and it is also difficult to dispense the powdered formulation because of its bulky and sticky nature."( Evaluation of Dantrolene Granules Extemporaneously Reformulated from Capsules in a Pharmacy.
Aoshima, H; Kagawa, Y; Maruyama, S; Miyazaki, Y; Tsuboi, A; Uchino, T, 2020
)
0.92
" Primary outcomes included a description of the form and dosage of dantrolene prescribed, the incidence of adverse effects after dantrolene use, and its efficacy for the treatment of cerebral vasospasm."( The Role of Parenteral Dantrolene in the Contemporary Management of Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review.
Nunna, RS; Ortiz, M; Qureshi, AI; Ravipati, K; Siddiq, F; Tran, A, 2022
)
1.27
" Our study provides dosing and adverse effect data as a basis for further randomized controlled clinical trials to determine the efficacy of oral dantrolene for symptomatic relief in MHS-related myopathies."( Oral Dantrolene for Myopathic Symptoms in Malignant Hyperthermia-Susceptible Patients: A 25-Year Retrospective Cohort Study of Adverse Effects and Tolerability.
Ibarra Moreno, CA; Jungbluth, H; Kraeva, N; Riazi, S; Voermans, NC; Zvaritch, E, 2023
)
1.62
"This study describes the development of an environmentally-friend optical nanosensor for the rapid spectrofluorimetric assessment of two nitro-compounds, namely nitrofurantoin and dantrolene in their dosage forms and plasma samples."( Turn-off fluorescence of S,N-doped carbon dots for determination of two nitro-containing drugs in dosage forms and human plasma.
Aboshabana, R; Belal, F; El Sharkasy, ME; Tolba, MM; Walash, MI, 2023
)
1.1
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
muscle relaxantA drug used to produce muscle relaxation (excepting neuromuscular blocking agents). Its primary clinical and therapeutic use is the treatment of muscle spasm and immobility associated with strains, sprains, and injuries of the back and, to a lesser degree, injuries to the neck. Also used for the treatment of a variety of clinical conditions that have in common only the presence of skeletal muscle hyperactivity, for example, the muscle spasms that can occur in multiple sclerosis.
ryanodine receptor antagonistnull
neuroprotective agentAny compound that can be used for the treatment of neurodegenerative disorders.
[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 (2)

ClassDescription
imidazolidine-2,4-dioneAn imidazolidinone with oxo groups at position 2 and 4.
hydrazoneCompounds having the structure R2C=NNR2, formally derived from aldehydes or ketones by replacing =O by =NNH2 (or substituted analogues).
[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 (8)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
phosphopantetheinyl transferaseBacillus subtilisPotency89.12510.141337.9142100.0000AID1490
TDP1 proteinHomo sapiens (human)Potency33.52780.000811.382244.6684AID686978; AID686979
Microtubule-associated protein tauHomo sapiens (human)Potency12.06270.180013.557439.8107AID1460
regulator of G-protein signaling 4Homo sapiens (human)Potency0.07520.531815.435837.6858AID504845
glucocerebrosidaseHomo sapiens (human)Potency22.38720.01268.156944.6684AID2101
lamin isoform A-delta10Homo sapiens (human)Potency6.30960.891312.067628.1838AID1487
[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)
Bile salt export pumpHomo sapiens (human)IC50 (µMol)145.50000.11007.190310.0000AID1449628
CDGSH iron-sulfur domain-containing protein 1Homo sapiens (human)IC50 (µMol)48.33000.73103.79949.0780AID1323834
CDGSH iron-sulfur domain-containing protein 1Homo sapiens (human)Ki2.06500.03101.20547.2910AID1323835
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (25)

Processvia Protein(s)Taxonomy
fatty acid metabolic processBile salt export pumpHomo sapiens (human)
bile acid biosynthetic processBile salt export pumpHomo sapiens (human)
xenobiotic metabolic processBile salt export pumpHomo sapiens (human)
xenobiotic transmembrane transportBile salt export pumpHomo sapiens (human)
response to oxidative stressBile salt export pumpHomo sapiens (human)
bile acid metabolic processBile salt export pumpHomo sapiens (human)
response to organic cyclic compoundBile salt export pumpHomo sapiens (human)
bile acid and bile salt transportBile salt export pumpHomo sapiens (human)
canalicular bile acid transportBile salt export pumpHomo sapiens (human)
protein ubiquitinationBile salt export pumpHomo sapiens (human)
regulation of fatty acid beta-oxidationBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transportBile salt export pumpHomo sapiens (human)
bile acid signaling pathwayBile salt export pumpHomo sapiens (human)
cholesterol homeostasisBile salt export pumpHomo sapiens (human)
response to estrogenBile salt export pumpHomo sapiens (human)
response to ethanolBile salt export pumpHomo sapiens (human)
xenobiotic export from cellBile salt export pumpHomo sapiens (human)
lipid homeostasisBile salt export pumpHomo sapiens (human)
phospholipid homeostasisBile salt export pumpHomo sapiens (human)
positive regulation of bile acid secretionBile salt export pumpHomo sapiens (human)
regulation of bile acid metabolic processBile salt export pumpHomo sapiens (human)
transmembrane transportBile salt export pumpHomo sapiens (human)
regulation of autophagyCDGSH iron-sulfur domain-containing protein 1Homo sapiens (human)
regulation of cellular respirationCDGSH iron-sulfur domain-containing protein 1Homo sapiens (human)
protein maturation by [2Fe-2S] cluster transferCDGSH iron-sulfur domain-containing protein 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (14)

Processvia Protein(s)Taxonomy
protein bindingBile salt export pumpHomo sapiens (human)
ATP bindingBile salt export pumpHomo sapiens (human)
ABC-type xenobiotic transporter activityBile salt export pumpHomo sapiens (human)
bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
canalicular bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transporter activityBile salt export pumpHomo sapiens (human)
ABC-type bile acid transporter activityBile salt export pumpHomo sapiens (human)
ATP hydrolysis activityBile salt export pumpHomo sapiens (human)
pyridoxal phosphate bindingCDGSH iron-sulfur domain-containing protein 1Homo sapiens (human)
identical protein bindingCDGSH iron-sulfur domain-containing protein 1Homo sapiens (human)
protein homodimerization activityCDGSH iron-sulfur domain-containing protein 1Homo sapiens (human)
metal ion bindingCDGSH iron-sulfur domain-containing protein 1Homo sapiens (human)
L-cysteine transaminase activityCDGSH iron-sulfur domain-containing protein 1Homo sapiens (human)
2 iron, 2 sulfur cluster bindingCDGSH iron-sulfur domain-containing protein 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (14)

Processvia Protein(s)Taxonomy
basolateral plasma membraneBile salt export pumpHomo sapiens (human)
Golgi membraneBile salt export pumpHomo sapiens (human)
endosomeBile salt export pumpHomo sapiens (human)
plasma membraneBile salt export pumpHomo sapiens (human)
cell surfaceBile salt export pumpHomo sapiens (human)
apical plasma membraneBile salt export pumpHomo sapiens (human)
intercellular canaliculusBile salt export pumpHomo sapiens (human)
intracellular canaliculusBile salt export pumpHomo sapiens (human)
recycling endosomeBile salt export pumpHomo sapiens (human)
recycling endosome membraneBile salt export pumpHomo sapiens (human)
extracellular exosomeBile salt export pumpHomo sapiens (human)
membraneBile salt export pumpHomo sapiens (human)
mitochondrionCDGSH iron-sulfur domain-containing protein 1Homo sapiens (human)
mitochondrial outer membraneCDGSH iron-sulfur domain-containing protein 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (114)

Assay IDTitleYearJournalArticle
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.
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID1148306Toxicity in albino mouse after 72 hrs1978Journal of medicinal chemistry, Jan, Volume: 21, Issue:1
Synthesis and comparative skeletal muscle relaxant activity of some 2,4-imidazolidinediones and their corresponding 5-hydroxy-2,4-imidazolidinediones.
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.
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
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).
AID1213389Ratio of AUC in wild-type FVB mouse blood in presence of GF120918 to AUC in wild-type FVB mouse blood at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID678716Inhibition of human CYP3A4 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using diethoxyfluorescein as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID1213406Apparent permeability from basolateral to apical side in human Caco2 cells at 5 uM after 2 hrs in presence of Ko143 BCRP-specific inhibitor2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
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).
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.
AID1213407Apparent permeability from apical to basolateral side in human Caco2 cells at 5 uM after 2 hrs in presence of GF120918 Pgp/Bcrp dual inhibitor2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID540212Mean residence time in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
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.
AID1701393Inhibition of RYR-1 R614C mutant (unknown origin) expressed in cells assessed as inhibition of store overload-induced Ca2+ release after 3 mins by microscopic analysis2021Bioorganic & medicinal chemistry, 01-01, Volume: 29Design, synthesis, and biological activity of novel semicarbazones as potent Ryanodine receptor1 inhibitors of Alzheimer's disease.
AID1213384Ratio of AUC in BCRP knockout FVB mouse CSF to AUC in wild-type FVB mouse CSF at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID540213Half life in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
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).
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).
AID1213380Ratio of AUC in MDR1A/1B/BCRP knockout FVB mouse blood to AUC in wild-type FVB mouse blood at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1213378Ratio of AUC in BCRP knockout FVB mouse blood to AUC in wild-type FVB mouse blood at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1079933Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is
AID1148303Induction of straub tail relaxation in albino mouse assessed as gain of righting reflex in 1 min1978Journal of medicinal chemistry, Jan, Volume: 21, Issue:1
Synthesis and comparative skeletal muscle relaxant activity of some 2,4-imidazolidinediones and their corresponding 5-hydroxy-2,4-imidazolidinediones.
AID1213383Ratio of AUC in MDR1A/1B/BCRP knockout FVB mouse brain to AUC in wild-type FVB mouse brain at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1557097Inhibition of RyR1 harboring R2163C mutant (unknown origin) stably expressed in HEK293 cells coexpressing R-CEPIA1er assessed as suppression in Ca2+ leakage from ER prestimulated with doxycycline for 24 to 28 hrs followed by compound addition at 100 secs 2019European journal of medicinal chemistry, Oct-01, Volume: 179Structural development of a type-1 ryanodine receptor (RyR1) Ca
AID1213395Ratio of AUC in wild-type FVB mouse CSF in presence of GF120918 to AUC in wild-type FVB mouse CSF at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1918192Inhibition of human OAT2 tv.1 variant expressed in HEK293 cells assessed as inhibition of [3H]cGMP uptake by scintillation analysis2022Journal of medicinal chemistry, 11-10, Volume: 65, Issue:21
Identification of Organic Anion Transporter 2 Inhibitors: Screening, Structure-Based Analysis, and Clinical Drug Interaction Risk Assessment.
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID678717Inhibition of human CYP3A4 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using 7-benzyloxyquinoline as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID1213377Inhibition of P-gp-mediated [3H]-digoxin transport in human Caco2 cells at 10 to 50 uM after 30 mins2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
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).
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
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.
AID678714Inhibition of human CYP2C19 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using 3-butyryl-7-methoxycoumarin as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
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).
AID1701391Inhibition of electric eel AChE at 5 uM using acetylthiocholine iodide as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured for 10 mins by Ellman's method relative to control2021Bioorganic & medicinal chemistry, 01-01, Volume: 29Design, synthesis, and biological activity of novel semicarbazones as potent Ryanodine receptor1 inhibitors of Alzheimer's disease.
AID1213371Efflux ratio of apparent permeability from basolateral to apical over apical to basolateral side in human Caco2 cells at 5 uM after 2 hrs2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1213369Apparent permeability from apical to basolateral side in human Caco2 cells at 5 uM after 2 hrs2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
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).
AID1213392Ratio of AUC in wild-type FVB mouse brain in presence of GF120918 to AUC in wild-type FVB mouse brain at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1701385Inhibition of RYR-1 R614C mutant (unknown origin) expressed in cells assessed as inhibition of store overload-induced Ca2+ release at 3 uM after 3 mins by fura-2AM dye based microscopic analysis relative to control2021Bioorganic & medicinal chemistry, 01-01, Volume: 29Design, synthesis, and biological activity of novel semicarbazones as potent Ryanodine receptor1 inhibitors of Alzheimer's disease.
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID1701384Inhibition of RYR-1 R614C mutant (unknown origin) expressed in cells assessed as inhibition of store overload-induced Ca2+ release at 0.1 uM after 3 mins by fura-2AM dye based microscopic analysis relative to control2021Bioorganic & medicinal chemistry, 01-01, Volume: 29Design, synthesis, and biological activity of novel semicarbazones as potent Ryanodine receptor1 inhibitors of Alzheimer's disease.
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.
AID625276FDA Liver Toxicity Knowledge Base Benchmark Dataset (LTKB-BD) drugs of most concern for DILI2011Drug discovery today, Aug, Volume: 16, Issue:15-16
FDA-approved drug labeling for the study of drug-induced liver injury.
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID1213394Ratio of AUC in wild-type FVB mouse CSF in presence of PSC833 to AUC in wild-type FVB mouse CSF at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1213382Ratio of AUC in MDR1A/1B knockout FVB mouse brain to AUC in wild-type FVB mouse brain at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
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.
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).
AID678722Covalent binding affinity to human liver microsomes assessed per mg of protein at 10 uM after 60 mins presence of NADPH2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID678721Metabolic stability in human liver microsomes assessed as GSH adduct formation at 100 uM after 90 mins by HPLC-MS analysis2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID1079931Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source]
AID1213385Ratio of AUC in MDR1A/1B knockout FVB mouse CSF to AUC in wild-type FVB mouse CSF at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID678712Inhibition of human CYP1A2 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using ethoxyresorufin as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID540210Clearance in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
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).
AID1213386Ratio of AUC in MDR1A/1B/BCRP knockout FVB mouse CSF to AUC in wild-type FVB mouse CSF at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1213379Ratio of AUC in MDR1A/1B knockout FVB mouse blood to AUC in wild-type FVB mouse blood at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1213393Ratio of AUC in wild-type FVB mouse CSF in presence of Ko143 to AUC in wild-type FVB mouse CSF at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1079936Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source]
AID1701390Kinetic aqueous solubility of the compound in PBS at pH 7.4 by turbidimetric analysis2021Bioorganic & medicinal chemistry, 01-01, Volume: 29Design, synthesis, and biological activity of novel semicarbazones as potent Ryanodine receptor1 inhibitors of Alzheimer's disease.
AID1323834Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by scintillation proximity assay2016Bioorganic & medicinal chemistry letters, 11-01, Volume: 26, Issue:21
Identification of small molecules that bind to the mitochondrial protein mitoNEET.
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
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.
AID1213390Ratio of AUC in wild-type FVB mouse brain in presence of Ko143 to AUC in wild-type FVB mouse brain at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1148308Inhibition of twitch in Charles River rat diaphragm at 60 mg/L after 5 mins1978Journal of medicinal chemistry, Jan, Volume: 21, Issue:1
Synthesis and comparative skeletal muscle relaxant activity of some 2,4-imidazolidinediones and their corresponding 5-hydroxy-2,4-imidazolidinediones.
AID1455188Efflux ratio of passive permeability in MDCK2-MDR1 cells transduced with BacMam2-BCRP at 3 uM after 90 mins by Transwell assay2018Journal of medicinal chemistry, 03-22, Volume: 61, Issue:6
Discovery of Novel 1-Cyclopentenyl-3-phenylureas as Selective, Brain Penetrant, and Orally Bioavailable CXCR2 Antagonists.
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
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).
AID678715Inhibition of human CYP2D6 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using 4-methylaminoethyl-7-methoxycoumarin as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID1148301Inhibition of gastrocnemius twitch in Sprague-Dawley rat at cumulative dose of 36.6 mg/kg, iv relative to control1978Journal of medicinal chemistry, Jan, Volume: 21, Issue:1
Synthesis and comparative skeletal muscle relaxant activity of some 2,4-imidazolidinediones and their corresponding 5-hydroxy-2,4-imidazolidinediones.
AID1213388Ratio of AUC in wild-type FVB mouse blood in presence of PSC833 to AUC in wild-type FVB mouse blood at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1148304Induction of muscle incoordination in mouse after 30 mins by rotarod test1978Journal of medicinal chemistry, Jan, Volume: 21, Issue:1
Synthesis and comparative skeletal muscle relaxant activity of some 2,4-imidazolidinediones and their corresponding 5-hydroxy-2,4-imidazolidinediones.
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).
AID1213376Inhibition of BCRP-mediated [3H]estrone-3-sulfate transport in human Caco2 cells assessed as efflux ratio of apparent permeability from basolateral to apical over apical to basolateral side at 10 to 50 uM after 30 mins2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1701386Inhibition of RYR-1 R614C mutant (unknown origin) expressed in cells assessed as inhibition of store overload-induced Ca2+ release at 10 uM after 3 mins by fura-2AM dye based microscopic analysis relative to control2021Bioorganic & medicinal chemistry, 01-01, Volume: 29Design, synthesis, and biological activity of novel semicarbazones as potent Ryanodine receptor1 inhibitors of Alzheimer's disease.
AID1148305Muscle relaxant efficacy index, ratio of ED50 for muscle incoordination in mouse to ED50 for induction of straub tail relaxation in albino mouse1978Journal of medicinal chemistry, Jan, Volume: 21, Issue:1
Synthesis and comparative skeletal muscle relaxant activity of some 2,4-imidazolidinediones and their corresponding 5-hydroxy-2,4-imidazolidinediones.
AID678713Inhibition of human CYP2C9 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using 7-methoxy-4-trifluoromethylcoumarin-3-acetic acid as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID1148300Induction of skeletal muscle relaxation in ip dosed albino mouse after 60 mins1978Journal of medicinal chemistry, Jan, Volume: 21, Issue:1
Synthesis and comparative skeletal muscle relaxant activity of some 2,4-imidazolidinediones and their corresponding 5-hydroxy-2,4-imidazolidinediones.
AID1079938Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source]
AID1148307Therapeutic index, ratio of LD50 for albino mouse to ED50 for induction of straub tail relaxation in albino mouse1978Journal of medicinal chemistry, Jan, Volume: 21, Issue:1
Synthesis and comparative skeletal muscle relaxant activity of some 2,4-imidazolidinediones and their corresponding 5-hydroxy-2,4-imidazolidinediones.
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).
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).
AID1148302Inhibition of gastrocnemius twitch in iv dosed Sprague-Dawley rat1978Journal of medicinal chemistry, Jan, Volume: 21, Issue:1
Synthesis and comparative skeletal muscle relaxant activity of some 2,4-imidazolidinediones and their corresponding 5-hydroxy-2,4-imidazolidinediones.
AID540209Volume of distribution at steady state in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID468443Inhibition of human FAAH at 1 uM2009Bioorganic & medicinal chemistry letters, Dec-01, Volume: 19, Issue:23
Mining biologically-active molecules for inhibitors of fatty acid amide hydrolase (FAAH): identification of phenmedipham and amperozide as FAAH inhibitors.
AID1213381Ratio of AUC in BCRP knockout FVB mouse brain to AUC in wild-type FVB mouse brain at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1213370Apparent permeability from basolateral to apical side in human Caco2 cells at 5 uM after 2 hrs2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1079941Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID1079935Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source]
AID588208Literature-mined public compounds from Lowe et al phospholipidosis modelling dataset2010Molecular pharmaceutics, Oct-04, Volume: 7, Issue:5
Predicting phospholipidosis using machine learning.
AID1148299Induction of skeletal muscle relaxation in po dosed albino mouse after 60 mins1978Journal of medicinal chemistry, Jan, Volume: 21, Issue:1
Synthesis and comparative skeletal muscle relaxant activity of some 2,4-imidazolidinediones and their corresponding 5-hydroxy-2,4-imidazolidinediones.
AID1323835Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis2016Bioorganic & medicinal chemistry letters, 11-01, Volume: 26, Issue:21
Identification of small molecules that bind to the mitochondrial protein mitoNEET.
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).
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID540235Phospholipidosis-negative literature compound
AID1213391Ratio of AUC in wild-type FVB mouse brain in presence of PSC833 to AUC in wild-type FVB mouse brain at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1213408Apparent permeability from basolateral to apical side in human Caco2 cells at 5 uM after 2 hrs in presence of GF120918 Pgp/Bcrp dual inhibitor2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1213405Apparent permeability from apical to basolateral side in human Caco2 cells at 5 uM after 2 hrs in presence of Ko143 BCRP-specific inhibitor2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
AID1449628Inhibition of human BSEP expressed in baculovirus transfected fall armyworm Sf21 cell membranes vesicles assessed as reduction in ATP-dependent [3H]-taurocholate transport into vesicles incubated for 5 mins by Topcount based rapid filtration method2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Mitigating the inhibition of human bile salt export pump by drugs: opportunities provided by physicochemical property modulation, in silico modeling, and structural modification.
AID1213387Ratio of AUC in wild-type FVB mouse blood in presence of Ko143 to AUC in wild-type FVB mouse blood at 2 mg/kg, iv measured at 5 to 180 mins by LC-MS/MS analysis2012Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 40, Issue:4
Cerebrospinal fluid can be used as a surrogate to assess brain exposures of breast cancer resistance protein and P-glycoprotein substrates.
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.
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.
AID588519A screen for compounds that inhibit viral RNA polymerase binding and polymerization activities2011Antiviral research, Sep, Volume: 91, Issue:3
High-throughput screening identification of poliovirus RNA-dependent RNA polymerase inhibitors.
AID540299A screen for compounds that inhibit the MenB enzyme of Mycobacterium tuberculosis2010Bioorganic & medicinal chemistry letters, Nov-01, Volume: 20, Issue:21
Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: novel antibacterial agents against Mycobacterium tuberculosis.
AID1508629Cell Viability qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1508628Confirmatory 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.
AID1508627Counterscreen qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: GLuc-NoTag assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (1,920)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990711 (37.03)18.7374
1990's446 (23.23)18.2507
2000's355 (18.49)29.6817
2010's293 (15.26)24.3611
2020's115 (5.99)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 82.25

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 Index82.25 (24.57)
Research Supply Index7.63 (2.92)
Research Growth Index4.45 (4.65)
Search Engine Demand Index149.63 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (82.25)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Trials55 (2.74%)5.53%
Reviews1 (4.35%)6.00%
Reviews196 (9.78%)6.00%
Case Studies0 (0.00%)4.05%
Case Studies443 (22.09%)4.05%
Observational0 (0.00%)0.25%
Observational0 (0.00%)0.25%
Other22 (95.65%)84.16%
Other1,311 (65.39%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (11)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Phase 3, Multi-Center, Double-Blind, Randomized, 2-Arm, Parallel Study to Assess the Efficacy and Safety of Ryanodex (EGL-4104) as Adjuvant Treatment in Subjects With Exertional Heat Stroke (EHS) [NCT03600376]Phase 317 participants (Actual)Interventional2018-08-19Completed
The Use of Dantrolene to Improve Analgesia in Posterior Lumbar Surgery [NCT03762109]Phase 2100 participants (Anticipated)Interventional2019-07-29Recruiting
Targeting Residual Activity By Precision, Biomarker-Guided Combination Therapies of Multiple Sclerosis (TRAP-MS) [NCT03109288]Phase 1/Phase 2250 participants (Anticipated)Interventional2017-08-11Recruiting
Dantrolene as a Treatment for Hyperthermia in Patients After Subarachnoidal Hemorrhage [NCT00796900]Phase 2/Phase 334 participants (Anticipated)Interventional2008-05-31Terminated(stopped due to organizationally not possible)
Dantrolene in the Treatment of Cerebral Vasospasm After Subarachnoid Hemorrhage - a Phase 1 Study [NCT00964548]Phase 1/Phase 210 participants (Actual)Interventional2007-07-31Completed
Phase 2, Multiple-Site, Open-Label, Randomized, 2-Group, Parallel Study to Assess the Efficacy and Safety of Ryanodex(R) (EGL-4101)as Adjuvant Treatment in Subjects With Psychostimulant Drug-Induced Toxicity (PDIT) [NCT03189433]Phase 22 participants (Actual)Interventional2017-08-12Terminated(stopped due to Limited enrollment)
The Mechanism of Human Non-Shivering Thermogenesis and Basal Metabolic Rate [NCT01950520]Phase 2134 participants (Anticipated)Interventional2014-02-07Recruiting
Phase 2, Single-Site, Open-Label, Randomized, 2-Arm Parallel Study to Assess the Efficacy and Safety of Ryanodex® (EGL-4104) as Adjuvant Treatment in Subjects With Exertional Heat Stroke (EHS) [NCT02513095]Phase 234 participants (Actual)Interventional2015-09-30Completed
A Randomized Controlled Trial of RyR2 Inhibition With Dantrolene and Susceptibility to Ventricular Arrhythmias in Patients With Structural Heart Disease. [NCT04134845]Phase 2/Phase 384 participants (Anticipated)Interventional2020-08-21Recruiting
A Phase 1b/2a Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome [NCT02829268]Phase 1/Phase 221 participants (Actual)Interventional2017-01-31Completed
Dantrolene in the Prevention and Treatment of Cerebral Vasospasm in Subarachnoid Hemorrhage [NCT01024972]Phase 1/Phase 231 participants (Actual)Interventional2009-10-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00964548 (3) [back to overview]Hemodynamic Parameters (Change From Baseline Systolic Blood Pressure (Pre-infusion) Over Time Until 135 Minutes Post-infusion)
NCT00964548 (3) [back to overview]Transcranial Doppler Mean Flow Velocity (Change From Baseline Mean Flow Velocity (Pre-infusion) Over Time Until 135 Minutes Post-infusion)
NCT00964548 (3) [back to overview]Transcranial Doppler Peak Systolic Velocity (Change From Baseline Peak Systolic Velocity (Pre-infusion) Over Time Until 135 Minutes Post-infusion)
NCT01024972 (3) [back to overview]Hyponatremia
NCT01024972 (3) [back to overview]In-hospital Mortality
NCT01024972 (3) [back to overview]Liver Toxicity
NCT02513095 (1) [back to overview]Number of Subjects Achieving Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) GCS ≥ 13
NCT03600376 (2) [back to overview]Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) GCS ≥ 13 [Time Frame: 90 Minutes Post-randomization]
NCT03600376 (2) [back to overview]Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration]

Hemodynamic Parameters (Change From Baseline Systolic Blood Pressure (Pre-infusion) Over Time Until 135 Minutes Post-infusion)

Systolic Blood Pressure (Change from baseline systolic blood pressure (pre-infusion) over time until 135 minutes post-infusion). (NCT00964548)
Timeframe: baseline until 135 minutes post-infusion

InterventionmmHg (Mean)
Dantrolene (Low Dose)-8
Dantrolene (High Dose)-3.4

[back to top]

Transcranial Doppler Mean Flow Velocity (Change From Baseline Mean Flow Velocity (Pre-infusion) Over Time Until 135 Minutes Post-infusion)

Mean flow velocities of vessel in vasospasm (Change from baseline mean flow velocity (pre-infusion) over time until 135 minutes post-infusion). (NCT00964548)
Timeframe: baseline until 135 minutes post-infusion

Interventioncm/s (Mean)
Dantrolene (Low Dose)-18
Dantrolene (High Dose)-13

[back to top]

Transcranial Doppler Peak Systolic Velocity (Change From Baseline Peak Systolic Velocity (Pre-infusion) Over Time Until 135 Minutes Post-infusion)

Peak Systolic Velocity of vessel in vasospasm (Change from baseline peak systolic velocity (pre-infusion) over time until 135 minutes post-infusion). (NCT00964548)
Timeframe: baseline until 135 minutes post-infusion

Interventioncm/s (Mean)
Dantrolene (Low Dose)-30
Dantrolene (High Dose)-26

[back to top]

Hyponatremia

Number of subjects who developed hyponatremia (sNa ≤132mmol/L) (NCT01024972)
Timeframe: Seven days

Interventionparticipants (Number)
Dantrolene7
Placebo10

[back to top]

In-hospital Mortality

Number of subjects who expired during hospitalization. (NCT01024972)
Timeframe: up to 90 days

Interventionparticipants (Number)
Dantrolene2
Placebo1

[back to top]

Liver Toxicity

Number of subjects who developed liver toxicity as evidenced by Liver Function Test elevation greater than 5 times the upper limit of normal. (NCT01024972)
Timeframe: 7 days

Interventionparticipants (Number)
Dantrolene1
Placebo0

[back to top]

Number of Subjects Achieving Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) GCS ≥ 13

"Number of subjects achieving a Glasgow Coma Scale(GCS) ≥ 13 at or prior to 90 minutes post-randomization. The Glasgow Coma Scale (GCS) is a reliable and objective way of recording the initial and subsequent level of consciousness in a person after a brain injury. The range of total GCS score is 3 to15 where a higher GCS score represents a better outcome. The scores of subscales are summed to determine the total score*. A GCS score of 13-15 is considered Mild impairment of consciousness; a GCS score of 9-12 is considered Moderate impairment of consciousness; and a GCS score of 3-8 is considered Severe.~*Subscales: Eyes Response -Spontaneous=4; To sound =3; To Pressure=2; None=1; not tested. Verbal Response- Oriented=5; Confused=4; Words=3; Sounds=2; None-1; Not tested. Motor Response: Obeys Commands=6; Localizes=5; Normal Flexion=4; Abnormal Flexion=3; Extension=2; None=1; Not tested." (NCT02513095)
Timeframe: 90 minutes post-randomization

InterventionParticipants (Count of Participants)
Ryanodex Plus Standard of Care5
Standard of Care2

[back to top]

Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) GCS ≥ 13 [Time Frame: 90 Minutes Post-randomization]

The GCS is a validated and reliable scale to evaluate level of consciousness in patients with acute brain injury. The scale assesses 3 functions: Eye Opening, Verbal Response, and Motor Response. GCS scores range from 15 (best) to 3 (worst). (NCT03600376)
Timeframe: 90 minutes post-randomization

InterventionParticipants (Count of Participants)
Ryanodex and Standard of Care4
Standard of Care Only (SOC)2

[back to top]

Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration]

The GCS is a validated and reliable scale to evaluate level of consciousness in patients with acute brain injury. The scale assesses 3 functions: Eye Opening, Verbal Response, and Motor Response. GCS scores range from 15 (best) to 3 (worst). (NCT03600376)
Timeframe: Treatment duration, up to 6 hours

,
InterventionParticipants (Count of Participants)
Pts. achieving GCS score ≥ 13 at 15 min post-randomizationPts. achieving GCS score ≥ 13 at 30 min. post-randomizationPts. achieving GCS score ≥ 13 after 45 min. post-randomizationPts. achieving GCS score ≥ 13 after 60 min. post-randomizationPts. achieving GCS score ≥ 13 after 75 min. post-randomizationPts. achieving GCS score ≥ 13 after 90 min. post-randomizationPts. achieving GCS score ≥ to 13 after 2 hr.. post-randomizationPts. achieving GCS score ≥ 13 after 4 hr. post-randomization/follow-up phasePts. achieving GCS score ≥ 13 at end of study or early termination
Ryanodex and Standard of Care111234555
Standard of Care Only (SOC)000122222

[back to top]