DANTROLENE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H10N4O5
Molecular Weight	314.253
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[O-][N+](=O)C1=CC=C(C=C1)C2=CC=C(O2)\C=N\N3CC(=O)NC3=O

InChI

InChIKey=OZOMQRBLCMDCEG-VIZOYTHASA-N

InChI=1S/C14H10N4O5/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)/b15-7+

HIDE SMILES / InChI

Molecular Formula	C14H10N4O5
Molecular Weight	314.253
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Ryanodine receptor 1 4 Target ID: P21817 Gene ID: 6261.0 Gene Symbol: RYR1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/15023108	Antagonist 2849		130.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic spasticity 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017443s043s046s048s049lbl.pdf	Primary		Approved 8583	DANTRIUM Approved Use In 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 Date 1974
Malignant hyperthermia 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017443s043s046s048s049lbl.pdf	Preventing		Approved 8583	DANTRIUM Approved Use In 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 Date 1974

C_max

Value	Dose	Co-administered	Analyte	Population
9 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205579s000lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205579s000lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.7 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017443s043s046s048s049lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205579s000lbl.pdf	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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 725 OAT3 747 MRP4 290	CYP1A1 389 CYP1A2 1197 CYP3A 220 BCRP 697

Drug as perpetrator

Target	Modality	Activity
OAT3 749	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28630284/	yes [IC50 0.3 uM]
OAT1 730	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28630284/	yes [IC50 1.89 uM]
MRP4 345	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28630284/	yes [IC50 5.29 uM]

Drug as victim

Target	Modality	Activity
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/22115838/	yes
CYP1A1 389	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/7902259/	yes
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/7902259/	yes
CYP3A 220	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/7902259/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4317	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4317
MolPort	MolPort-003-846-133	https://www.molport.com/shop/molecule-link/MolPort-003-846-133
ZINC	ZINC000252679615	http://zinc15.docking.org/substances/ZINC000252679615

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	25051504
Caffeine induces cardiomyocyte hypertrophy via p300 and CaMKII pathways.	2014-09-25	25093688
Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action.	2014	25058030
Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model.	2013-12	24052561
Tributyltin-induced endoplasmic reticulum stress and its Ca(2+)-mediated mechanism.	2013-10-01	23743301
Antispasmodic effect of shakuyakukanzoto extract on experimental muscle cramps in vivo: role of the active constituents of Glycyrrhizae radix.	2013-01-09	23164761
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	23183170
Stimulation of cytosolic and mitochondrial calcium mobilization by indomethacin in Caco-2 cells: modulation by the polyphenols quercetin, resveratrol and rutin.	2012-12	23022152
Ryanodine receptors contribute to bile acid-induced pathological calcium signaling and pancreatitis in mice.	2012-06-15	22517774
Diphenyl ditelluride induces hypophosphorylation of intermediate filaments through modulation of DARPP-32-dependent pathways in cerebral cortex of young rats.	2012-02	21863293
Cross-talk among intracellular signaling pathways mediates the diphenyl ditelluride actions on the hippocampal cytoskeleton of young rats.	2011-10-17	21879721
Dantrolene, a therapeutic agent for malignant hyperthermia, inhibits catecholaminergic polymorphic ventricular tachycardia in a RyR2(R2474S/+) knock-in mouse model.	2010-11	20944434
Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition.	2008-12	18493746
Cellular imaging predictions of clinical drug-induced liver injury.	2008-09	18524759
Quantitative investigation of the role of breast cancer resistance protein (Bcrp/Abcg2) in limiting brain and testis penetration of xenobiotic compounds.	2008-06	18322075
Transitional cell carcinoma in the paediatric population: be aware of unusual aetiologies.	2007-11	17924939
A novel compound heterozygous dysferlin mutation in Miyoshi myopathy siblings responding to dantrolene.	2007-11	17868276
Identification of functional type 1 ryanodine receptors in human dendritic cells.	2007-10-19	17707769
KATP channel knockout worsens myocardial calcium stress load in vivo and impairs recovery in stunned heart.	2007-04	17189350
Neuroleptic malignant syndrome with delayed onset of fever following risperidone administration.	2006-12	17119106
Doxorubicin-induced reactive oxygen species generation and intracellular Ca2+ increase are reciprocally modulated in rat cardiomyocytes.	2006-10-31	17079870
[A case of malignant syndrome triggered by the use of haloperidol and chrorpromazine].	1997-04	9128030
Malignant hyperthermia induced by general anesthesia for bone marrow harvesting.	1997-03	9052921
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	9017254
Dantrolene treatment of opioid-induced myoclonus.	1995-12	7486124
Induction or protection of limbic seizures in mice by mGluR subtype selective agonists.	1995-08	8532155
Clinical effects of intravenously administered dantrolene.	1995-03	7861811
[Clinical study of neuroleptic malignant syndrome in demented patients--examination of our case and reported cases].	1994-09	7999444
[Freeman-Sheldon syndrome: generalized muscular rigidity after anesthetic induction].	1994-05-01	8059048
Management of neuroleptic malignant syndrome--a series of eight cases.	1993-02	8101521
Successful treatment of an episode of malignant hyperthermia using a large dose of dantrolene.	1993-01-01	8442973
[Successful treatment of levodopa-induced neuroleptic malignant syndrome (NMS) with disseminated intravascular coagulation (DIC) in a patient with Parkinson's disease].	1991-01	2044308
Treatment of lethal catatonia with electroconvulsive therapy and dantrolene sodium: a case report.	1990-07	2399829
Trimipramine-induced neuroleptic malignant syndrome after transient psychogenic polydipsia in one patient.	1989-04	2925603
Sudden bilateral sensorineural hearing loss during treatment with dantrolene sodium (dantrium).	1988-01	3343565
Prevention of amphotericin B-induced rigors by dantrolene.	1986-08	3729640
[Cardiac failure caused by an overdose of dantrolene].	1986	3826797
Pneumonitis, pleural effusion and pericarditis following treatment with dantrolene.	1984-05	6736987
Hyperkalemia and cardiovascular collapse after verapamil and dantrolene administration in swine.	1984-05	6711841
Neuroleptic malignant syndrome: successful treatment with dantrolene and bromocriptine.	1983-07	6614876
Beneficial effects of dantrolene in the treatment of neuroleptic malignant syndrome: a report of two cases.	1983-04	6682201
Neuroleptic malignant syndrome: response to dantrolene sodium.	1983-02	6824251
Treatment of neuroleptic malignant syndrome with dantrolene.	1982-07-03	6123782
[Neuroleptic malignant syndrome. Beneficial effects of dantrolene on hyperthermia and hypertonia (author's transl)].	1982-03-27	7079122
Dantrolene and lymphocytic lymphoma.	1980-04	6893628
Pleuropericardial reaction to treatment with dantrolene.	1979-12-21	501885
Dantrolene and suxamethonium. The effect of pre-operative dantrolene on the action of suxamethonium.	1979-02	375768
Hepatitis from dantrolene sodium.	1979-01	761834
Dantrolene-associated hepatic injury. Incidence and character.	1977-04	838213
Dantrolene hepatitis.	1976-04-12	946274

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:34:09 GMT 2025` Edited by `admin` on `Mon Mar 31 17:34:09 GMT 2025`
Record UNII	F64QU97QCR
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DANTROLENE

Official Name

English

DANTROLENE [HSDB]

Preferred Name

English

DANTROLENE [USP-RS]

Common Name

English

DANTROLENE [USAN]

Common Name

English

Dantrolene [WHO-DD]

Common Name

English

2,4-IMIDAZOLIDINEDIONE, 1-(((5-(4-NITROPHENYL)-2-FURANYL)METHYLENE)AMINO)-

Systematic Name

English

dantrolene [INN]

Common Name

English

DANTROLENE [VANDF]

Common Name

English

DANTROLENE [MI]

Common Name

English

1-(((5-(4-NITROPHENYL)-2-FURYL)METHYLENE)AMINO)IMIDAZOLIDINE-2,4-DIONE

Systematic Name

English

Classification Tree Code System Code

NDF-RT

N0000175735