Details
Stereochemistry | ACHIRAL |
Molecular Formula | C14H9N4O5.Na |
Molecular Weight | 336.2348 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].[O-][N+](=O)C1=CC=C(C=C1)C2=CC=C(O2)\C=N\N3CC(=O)[N-]C3=O
InChI
InChIKey=KSRLIXGNPXAZHD-HAZZGOGXSA-M
InChI=1S/C14H10N4O5.Na/c19-13-8-17(14(20)16-13)15-7-11-5-6-12(23-11)9-1-3-10(4-2-9)18(21)22;/h1-7H,8H2,(H,16,19,20);/q;+1/p-1/b15-7+;
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/15023108Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/9341133, http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017443s043s046s048s049lbl.pdf
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15023108
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/9341133, http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017443s043s046s048s049lbl.pdf
Dantrolene is a drug which was approved by FDA for the treatment of chronic spasticity and malignant hyperthermia (a rare life-threatening clinical syndrome). Dantrolene effect was shown both in vivo and in vitro and proved to be mediated by interaction with Ryanodine receptor 1. The drug has a potential for hepatotoxicity and should be used as indicated in the label.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15105208
Curator's Comment: Dantrolene crosses the blood-brain barrier and produces mild sedation
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: P21817 Gene ID: 6261.0 Gene Symbol: RYR1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/15023108 |
130.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | DANTRIUM Approved UseIn Chronic Spasticity: Dantrium is indicated in controlling the manifestations of clinical spasticity resulting from upper motor neuron disorders (e.g., spinal cord injury, stroke, cerebral palsy, or multiple sclerosis). In Malignant Hyperthermia: Oral Dantrium is also indicated preoperatively to prevent or attenuate the development of signs of malignant hyperthermia in known, or strongly suspect, malignant hyperthermia susceptible patients who require anesthesia and/or surgery. Launch Date1974 |
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Preventing | DANTRIUM Approved UseIn Chronic Spasticity: Dantrium is indicated in controlling the manifestations of clinical spasticity resulting from upper motor neuron disorders (e.g., spinal cord injury, stroke, cerebral palsy, or multiple sclerosis). In Malignant Hyperthermia: Oral Dantrium is also indicated preoperatively to prevent or attenuate the development of signs of malignant hyperthermia in known, or strongly suspect, malignant hyperthermia susceptible patients who require anesthesia and/or surgery. Launch Date1974 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
9 μg/mL |
2.5 mg/kg single, intravenous dose: 2.5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
DANTROLENE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
77.7 μg × h/mL |
2.5 mg/kg single, intravenous dose: 2.5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
DANTROLENE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
8.7 h |
100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
DANTROLENE blood | Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
10.8 h |
2.5 mg/kg single, intravenous dose: 2.5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
DANTROLENE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
25 mg 1 times / day steady, oral (starting) Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Hepatitis, Diarrhea... AEs leading to discontinuation/dose reduction: Hepatitis Sources: Diarrhea |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Diarrhea | Disc. AE | 25 mg 1 times / day steady, oral (starting) Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Hepatitis | Disc. AE | 25 mg 1 times / day steady, oral (starting) Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
Dantrolene hepatitis. | 1976 Apr 12 |
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Hepatitis from dantrolene sodium. | 1979 Jan |
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Treatment of neuroleptic malignant syndrome with dantrolene. | 1982 Jul 3 |
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Beneficial effects of dantrolene in the treatment of neuroleptic malignant syndrome: a report of two cases. | 1983 Apr |
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Neuroleptic malignant syndrome: successful treatment with dantrolene and bromocriptine. | 1983 Jul |
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Pneumonitis, pleural effusion and pericarditis following treatment with dantrolene. | 1984 May |
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Hyperkalemia and cardiovascular collapse after verapamil and dantrolene administration in swine. | 1984 May |
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[Cardiac failure caused by an overdose of dantrolene]. | 1986 |
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Prevention of amphotericin B-induced rigors by dantrolene. | 1986 Aug |
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Sudden bilateral sensorineural hearing loss during treatment with dantrolene sodium (dantrium). | 1988 Jan |
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Treatment of lethal catatonia with electroconvulsive therapy and dantrolene sodium: a case report. | 1990 Jul |
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Neuroleptic malignant syndrome induced by domperidone. | 1992 Jun |
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Successful treatment of levodopa-induced neuroleptic malignant syndrome (NMS) and disseminated intravascular coagulation (DIC) in a patient with Parkinson's disease. | 1992 Nov |
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Successful treatment of an episode of malignant hyperthermia using a large dose of dantrolene. | 1993 Jan-Feb |
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Induction or protection of limbic seizures in mice by mGluR subtype selective agonists. | 1995 Aug |
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Dantrolene treatment of opioid-induced myoclonus. | 1995 Dec |
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Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level. | 1996 Dec 16 |
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[A case of malignant syndrome triggered by the use of haloperidol and chrorpromazine]. | 1997 Apr |
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Malignant hyperthermia induced by general anesthesia for bone marrow harvesting. | 1997 Mar |
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Suxamethonium, masseter spasm and later malignant hyperthermia. | 1998 Nov |
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Dantrolene inhibition of ryanodine receptor Ca2+ release channels. Molecular mechanism and isoform selectivity. | 2001 Apr 27 |
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Atypical neuroleptic malignant syndrome caused by clozapine and venlafaxine: early brief treatment with dantrolene. | 2004 Jul |
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Drug-induced liver injury. | 2004 Mar 1 |
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Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
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An unusual case of Dantrolene sodium-induced urinary retention in post-traumatic minimally responsive state. | 2005 Nov |
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Prevention of succinylcholine-induced fasciculation and myalgia: a meta-analysis of randomized trials. | 2005 Oct |
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A novel compound heterozygous dysferlin mutation in Miyoshi myopathy siblings responding to dantrolene. | 2007 Nov |
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Cross-talk among intracellular signaling pathways mediates the diphenyl ditelluride actions on the hippocampal cytoskeleton of young rats. | 2011 Oct 17 |
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Stimulation of cytosolic and mitochondrial calcium mobilization by indomethacin in Caco-2 cells: modulation by the polyphenols quercetin, resveratrol and rutin. | 2012 Dec |
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Diphenyl ditelluride induces hypophosphorylation of intermediate filaments through modulation of DARPP-32-dependent pathways in cerebral cortex of young rats. | 2012 Feb |
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Ryanodine receptors contribute to bile acid-induced pathological calcium signaling and pancreatitis in mice. | 2012 Jun 15 |
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Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. | 2013 Dec |
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Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action. | 2014 |
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Comparative gene and protein expression analyses of a panel of cytokines in acute and chronic drug-induced liver injury in rats. | 2014 Oct 3 |
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Caffeine induces cardiomyocyte hypertrophy via p300 and CaMKII pathways. | 2014 Sep 25 |
Sample Use Guides
For Use in Chronic Spasticity: 25 mg once daily for seven days, then 25 mg t.i.d. for seven days, 50 mg t.i.d. for seven days, 100 mg t.i.d. (adults). For Malignant Hyperthermia: administer 4 to 8 mg/kg/day of oral drug in 3 or 4 divided doses for one or two days prior to surgery, with the last dose being given approximately 3 to 4 hours before scheduled surgery with a minimum of water.
Route of Administration:
Oral
Whole skeletal muscle fascicles were incubated with dantrolene at concentrations of 5, 15 and 25 uM. Dantrolene inhibited twitch tensions of skeletal muscle fascicles, probably by indirectly preventing the release of calcium from the SR.
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ACTIVE MOIETY
SUBSTANCE RECORD