U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of DANTROLENE

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
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

Curator's Comment: Dantrolene crosses the blood-brain barrier and produces mild sedation

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P21817
Gene ID: 6261.0
Gene Symbol: RYR1
Target Organism: Homo sapiens (Human)
130.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

1.27440003E11
Preventing
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

1.27440003E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse 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
Disc. AE: Hepatitis, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Hepatitis
Diarrhea
Sources:
AEs

AEs

AESignificanceDosePopulation
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
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
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 0.3 uM]
yes [IC50 1.89 uM]
yes [IC50 5.29 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
Treatment of spastic cerebral-palsied children with sodium dantrolene.
1975 Dec
Letter: Hallucinations associated with dantrolene sodium therapy.
1975 Jan 25
Dantrolene hepatitis.
1976 Apr 12
Hepatitis from dantrolene sodium.
1979 Jan
Dantrolene and lymphocytic lymphoma.
1980 Apr
[Neuroleptic malignant syndrome. Beneficial effects of dantrolene on hyperthermia and hypertonia (author's transl)].
1982 Mar 27
Neuroleptic malignant syndrome: response to dantrolene sodium.
1983 Feb
Pneumonitis, pleural effusion and pericarditis following treatment with dantrolene.
1984 May
[Cardiac failure caused by an overdose of dantrolene].
1986
Neuroleptic malignant syndrome induced by domperidone.
1992 Jun
Successful treatment of levodopa-induced neuroleptic malignant syndrome (NMS) and disseminated intravascular coagulation (DIC) in a patient with Parkinson's disease.
1992 Nov
Successful treatment of an episode of malignant hyperthermia using a large dose of dantrolene.
1993 Jan-Feb
[Freeman-Sheldon syndrome: generalized muscular rigidity after anesthetic induction].
1994 May-Jun
Dantrolene treatment of opioid-induced myoclonus.
1995 Dec
[A case of malignant syndrome triggered by the use of haloperidol and chrorpromazine].
1997 Apr
Vesl/Homer proteins regulate ryanodine receptor type 2 function and intracellular calcium signaling.
2003 Sep
Atypical neuroleptic malignant syndrome caused by clozapine and venlafaxine: early brief treatment with dantrolene.
2004 Jul
Drug-induced liver injury.
2004 Mar 1
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Prevention of succinylcholine-induced fasciculation and myalgia: a meta-analysis of randomized trials.
2005 Oct
Early bicarbonate loading and dantroline for ziprasidone/haloperidol-induced neuroleptic malignant syndrome.
2006 Apr
Insulin-like growth factors (IGF) I and II utilize different calcium signaling pathways in a primary human parathyroid cell culture model.
2006 Mar
KATP channel knockout worsens myocardial calcium stress load in vivo and impairs recovery in stunned heart.
2007 Apr
Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition.
2008 Dec
Quantitative investigation of the role of breast cancer resistance protein (Bcrp/Abcg2) in limiting brain and testis penetration of xenobiotic compounds.
2008 Jun
Cellular imaging predictions of clinical drug-induced liver injury.
2008 Sep
Dantrolene, a therapeutic agent for malignant hyperthermia, inhibits catecholaminergic polymorphic ventricular tachycardia in a RyR2(R2474S/+) knock-in mouse model.
2010 Nov
Stimulation of cytosolic and mitochondrial calcium mobilization by indomethacin in Caco-2 cells: modulation by the polyphenols quercetin, resveratrol and rutin.
2012 Dec
Patents

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
In Vitro Use Guide
Sources: www.ncbi.nlm.nih.gov/pubmed/6704779
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 Fri Dec 15 14:59:19 UTC 2023
Edited
by admin
on Fri Dec 15 14:59:19 UTC 2023
Record UNII
F64QU97QCR
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DANTROLENE
HSDB   INN   MI   USAN   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official 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 [HSDB]
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
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
LIVERTOX NBK548144
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
NDF-RT N0000008953
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
WHO-ATC M03CA01
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
FDA ORPHAN DRUG 713319
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
WHO-VATC QM03CA01
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
NCI_THESAURUS C29696
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
NDF-RT N0000175738
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
Code System Code Type Description
DRUG CENTRAL
780
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
EVMPD
SUB06903MIG
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
ChEMBL
CHEMBL1201288
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
FDA UNII
F64QU97QCR
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
NDF-RT
N0000008953
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY Decreased Striated Muscle Contraction [PE]
NCI_THESAURUS
C61697
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
PUBCHEM
6914273
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
CAS
833480-90-3
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
ALTERNATIVE
EPA CompTox
DTXSID7022881
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
MESH
D003620
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
RS_ITEM_NUM
1163140
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
WIKIPEDIA
DANTROLENE
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
DRUG BANK
DB01219
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
CAS
7261-97-4
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
LACTMED
Dantrolene
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
MERCK INDEX
m4085
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY Merck Index
SMS_ID
100000083439
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
NDF-RT
N0000175735
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY Decreased Striated Muscle Tone [PE]
ECHA (EC/EINECS)
230-684-8
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
CHEBI
4317
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
IUPHAR
4172
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
HSDB
3050
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
RXCUI
3105
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY RxNorm
INN
2317
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
DAILYMED
F64QU97QCR
Created by admin on Fri Dec 15 14:59:19 UTC 2023 , Edited by admin on Fri Dec 15 14:59:19 UTC 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
Related Record Type Details
METABOLITE -> PARENT
MAJOR
METABOLITE -> PARENT
METABOLITE -> PARENT
Related Record Type Details
ACTIVE MOIETY