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+;
DescriptionCurator'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
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.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: P21817 Gene ID: 6261.0 Gene Symbol: RYR1 Target Organism: Homo sapiens (Human) |
130.0 nM [Ki] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| 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 |
|||
| 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 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Comparative gene and protein expression analyses of a panel of cytokines in acute and chronic drug-induced liver injury in rats. | 2014-10-03 |
|
| Caffeine induces cardiomyocyte hypertrophy via p300 and CaMKII pathways. | 2014-09-25 |
|
| Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action. | 2014 |
|
| Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. | 2013-12 |
|
| Tributyltin-induced endoplasmic reticulum stress and its Ca(2+)-mediated mechanism. | 2013-10-01 |
|
| Antispasmodic effect of shakuyakukanzoto extract on experimental muscle cramps in vivo: role of the active constituents of Glycyrrhizae radix. | 2013-01-09 |
|
| The calcium signaling pathway regulates leydig cell steroidogenesis through a transcriptional cascade involving the nuclear receptor NR4A1 and the steroidogenic acute regulatory protein. | 2013-01 |
|
| Stimulation of cytosolic and mitochondrial calcium mobilization by indomethacin in Caco-2 cells: modulation by the polyphenols quercetin, resveratrol and rutin. | 2012-12 |
|
| Ryanodine receptors contribute to bile acid-induced pathological calcium signaling and pancreatitis in mice. | 2012-06-15 |
|
| Diphenyl ditelluride induces hypophosphorylation of intermediate filaments through modulation of DARPP-32-dependent pathways in cerebral cortex of young rats. | 2012-02 |
|
| Cross-talk among intracellular signaling pathways mediates the diphenyl ditelluride actions on the hippocampal cytoskeleton of young rats. | 2011-10-17 |
|
| Dantrolene, a therapeutic agent for malignant hyperthermia, inhibits catecholaminergic polymorphic ventricular tachycardia in a RyR2(R2474S/+) knock-in mouse model. | 2010-11 |
|
| Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition. | 2008-12 |
|
| Cellular imaging predictions of clinical drug-induced liver injury. | 2008-09 |
|
| Quantitative investigation of the role of breast cancer resistance protein (Bcrp/Abcg2) in limiting brain and testis penetration of xenobiotic compounds. | 2008-06 |
|
| Transitional cell carcinoma in the paediatric population: be aware of unusual aetiologies. | 2007-11 |
|
| A novel compound heterozygous dysferlin mutation in Miyoshi myopathy siblings responding to dantrolene. | 2007-11 |
|
| Identification of functional type 1 ryanodine receptors in human dendritic cells. | 2007-10-19 |
|
| KATP channel knockout worsens myocardial calcium stress load in vivo and impairs recovery in stunned heart. | 2007-04 |
|
| Neuroleptic malignant syndrome with delayed onset of fever following risperidone administration. | 2006-12 |
|
| Doxorubicin-induced reactive oxygen species generation and intracellular Ca2+ increase are reciprocally modulated in rat cardiomyocytes. | 2006-10-31 |
|
| [A case of malignant syndrome triggered by the use of haloperidol and chrorpromazine]. | 1997-04 |
|
| Malignant hyperthermia induced by general anesthesia for bone marrow harvesting. | 1997-03 |
|
| 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. | 1996-12-16 |
|
| Dantrolene treatment of opioid-induced myoclonus. | 1995-12 |
|
| Induction or protection of limbic seizures in mice by mGluR subtype selective agonists. | 1995-08 |
|
| Clinical effects of intravenously administered dantrolene. | 1995-03 |
|
| [Clinical study of neuroleptic malignant syndrome in demented patients--examination of our case and reported cases]. | 1994-09 |
|
| [Freeman-Sheldon syndrome: generalized muscular rigidity after anesthetic induction]. | 1994-05-01 |
|
| Management of neuroleptic malignant syndrome--a series of eight cases. | 1993-02 |
|
| Successful treatment of an episode of malignant hyperthermia using a large dose of dantrolene. | 1993-01-01 |
|
| [Successful treatment of levodopa-induced neuroleptic malignant syndrome (NMS) with disseminated intravascular coagulation (DIC) in a patient with Parkinson's disease]. | 1991-01 |
|
| Treatment of lethal catatonia with electroconvulsive therapy and dantrolene sodium: a case report. | 1990-07 |
|
| Trimipramine-induced neuroleptic malignant syndrome after transient psychogenic polydipsia in one patient. | 1989-04 |
|
| Sudden bilateral sensorineural hearing loss during treatment with dantrolene sodium (dantrium). | 1988-01 |
|
| Prevention of amphotericin B-induced rigors by dantrolene. | 1986-08 |
|
| [Cardiac failure caused by an overdose of dantrolene]. | 1986 |
|
| Pneumonitis, pleural effusion and pericarditis following treatment with dantrolene. | 1984-05 |
|
| Hyperkalemia and cardiovascular collapse after verapamil and dantrolene administration in swine. | 1984-05 |
|
| Neuroleptic malignant syndrome: successful treatment with dantrolene and bromocriptine. | 1983-07 |
|
| Beneficial effects of dantrolene in the treatment of neuroleptic malignant syndrome: a report of two cases. | 1983-04 |
|
| Neuroleptic malignant syndrome: response to dantrolene sodium. | 1983-02 |
|
| Treatment of neuroleptic malignant syndrome with dantrolene. | 1982-07-03 |
|
| [Neuroleptic malignant syndrome. Beneficial effects of dantrolene on hyperthermia and hypertonia (author's transl)]. | 1982-03-27 |
|
| Dantrolene and lymphocytic lymphoma. | 1980-04 |
|
| Pleuropericardial reaction to treatment with dantrolene. | 1979-12-21 |
|
| Dantrolene and suxamethonium. The effect of pre-operative dantrolene on the action of suxamethonium. | 1979-02 |
|
| Hepatitis from dantrolene sodium. | 1979-01 |
|
| Dantrolene-associated hepatic injury. Incidence and character. | 1977-04 |
|
| Dantrolene hepatitis. | 1976-04-12 |
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
