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Details

Stereochemistry ACHIRAL
Molecular Formula 2C14H9N4O5.2Na.7H2O
Molecular Weight 798.5766
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 2
Charge 0

SHOW SMILES / InChI
Structure of DANTROLENE SODIUM

SMILES

O.O.O.O.O.O.O.[Na+].[Na+].[O-][N+](=O)C1=CC=C(C=C1)C2=CC=C(O2)\C=N\N3CC(=O)[N-]C3=O.[O-][N+](=O)C4=CC=C(C=C4)C5=CC=C(O5)\C=N\N6CC(=O)[N-]C6=O

InChI

InChIKey=LTWQNYPDAUSXBC-CDJGKPBYSA-L
InChI=1S/2C14H10N4O5.2Na.7H2O/c2*19-13-8-17(14(20)16-13)15-7-11-5-6-12(23-11)9-1-3-10(4-2-9)18(21)22;;;;;;;;;/h2*1-7H,8H2,(H,16,19,20);;;7*1H2/q;;2*+1;;;;;;;/p-2/b2*15-7+;;;;;;;;;

HIDE SMILES / InChI
Molecular Formula Na
Molecular Weight 22.9898
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
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
Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
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

CNS Active
3913
Curator's Comment: Dantrolene crosses the blood-brain barrier and produces mild sedation

Originator

Approval Year

1974
168
Targets

Targets

Primary TargetPharmacologyConditionPotency
Ryanodine receptor 1
4
Target ID: P21817
Gene ID: 6261.0
Gene Symbol: RYR1
Target Organism: Homo sapiens (Human)
Antagonist
2778
 130.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
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
Approved
8429
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017443s043s046s048s049lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017443s043s046s048s049lbl.pdf
Disc. AE: Hepatitis, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Hepatitis
Diarrhea
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017443s043s046s048s049lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017443s043s046s048s049lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017443s043s046s048s049lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017443s043s046s048s049lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017443s043s046s048s049lbl.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
OAT1
599

OAT3
642

MRP4
204
CYP1A1
349

CYP1A2
1054

CYP3A
191

BCRP
561
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
OAT3
644
 yes [IC50 0.3 uM]
OAT1
603
 yes [IC50 1.89 uM]
MRP4
238
 yes [IC50 5.29 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
BCRP
561
 yes
CYP1A1
349
 yes
CYP1A2
1054
 yes
CYP3A
191
 yes
Sourcing

Sourcing

Vendor/AggregatorIDURL
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

PubMed

TitleDatePubMed
Letter: Hallucinations associated with dantrolene sodium therapy.
1975 Jan 25
Pleuropericardial reaction to treatment with dantrolene.
1979 Dec 21
Treatment of lethal catatonia with electroconvulsive therapy and dantrolene sodium: a case report.
1990 Jul
Induction or protection of limbic seizures in mice by mGluR subtype selective agonists.
1995 Aug
Suxamethonium, masseter spasm and later malignant hyperthermia.
1998 Nov
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
The protective effect of dantrolene on ischemic neuronal cell death is associated with reduced expression of endoplasmic reticulum stress markers.
2005 Jun 28
An unusual case of Dantrolene sodium-induced urinary retention in post-traumatic minimally responsive state.
2005 Nov
Postoperative hyperthermia of unknown origin treated with dantrolene sodium.
2005 Spring
Secretion of brain-derived neurotrophic factor from brain microvascular endothelial cells.
2006 Mar
Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action.
2014
Patents

Patents

JP2002537317A
97
JP2006502081A
20
JP2007308403A
3
JP2010521465A
6
JPH01128923A
3
JPH05201879A
3
JPH06157248A
3
JPH06263636A
3
JPS5320413A
3

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
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 15:24:38 UTC 2023
Edited
by admin
on Fri Dec 15 15:24:38 UTC 2023
Record UNII
287M0347EV
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DANTROLENE SODIUM
MART.   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
DANTAMACRIN
Brand Name English
NSC-758403
Code English
Dantrolene sodium hemiheptahydrate [WHO-DD]
Common Name English
F-440
Code English
DANTRIUM
Brand Name English
DANTROLENE SODIUM HEMIHEPTAHYDRATE
Common Name English
DANTROLENE SODIUM HYDRATE
JAN  
Common Name English
Dantrolene sodium [WHO-DD]
Common Name English
DANTROLENE SODIUM HEPTAHYDRATE
Common Name English
DANTROLEN
Brand Name English
2,4-IMIDAZOLIDINEDIONE, 1-(((5-(4-NITROPHENYL)-2-FURANYL)METHYLENE)AMINO)-, SODIUM SALT, HYDRATE (2:7)
Common Name English
DANTROLENE SODIUM SALT HEMIHEPTAHYDRATE
MI  
Common Name English
DANTROLENE SODIUM [MART.]
Common Name English
DANTROLENE SODIUM [ORANGE BOOK]
Common Name English
DANTROLENE SODIUM [USAN]
Common Name English
DANTROLENE SODIUM HYDRATE [JAN]
Common Name English
DANTROLENE SODIUM [USP-RS]
Common Name English
1-((5-(P-NITROPHENYL)FURFURYLIDENE)AMINO)HYDANTOIN SODIUM SALT HYDRATE
Common Name English
DANTROLENE SODIUM [VANDF]
Common Name English
DANTROLENE SODIUM [USP MONOGRAPH]
Common Name English
DANTROLENE SODIUM SALT HEMIHEPTAHYDRATE [MI]
Common Name English
RYANODEX
Brand Name English
Classification Tree Code System Code
EU-Orphan Drug EU/3/16/1800
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
FDA ORPHAN DRUG 23287
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
FDA ORPHAN DRUG 179703
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
FDA ORPHAN DRUG 377512
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
NCI_THESAURUS C29696
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
FDA ORPHAN DRUG 474515
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
Code System Code Type Description
ChEMBL
CHEMBL1201288
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY
DRUG BANK
DBSALT000397
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY
NCI_THESAURUS
C61698
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY
PUBCHEM
9568637
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY
RS_ITEM_NUM
1163151
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY
EVMPD
SUB33252
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
ALTERNATIVE
DAILYMED
287M0347EV
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY
CAS
24868-20-0
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY
EVMPD
SUB01553MIG
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY
NSC
758403
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY
CHEBI
184644
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY
FDA UNII
287M0347EV
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY
SMS_ID
100000126026
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY
RXCUI
3106
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY RxNorm
EPA CompTox
DTXSID401017218
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY
CHEBI
4318
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY
MERCK INDEX
m4085
Created by admin on Fri Dec 15 15:24:38 UTC 2023 , Edited by admin on Fri Dec 15 15:24:38 UTC 2023
PRIMARY Merck Index
Related Record Type Details
Structure of DANTROLENE
PARENT -> SALT/SOLVATE
Structure of DANTROLENE SODIUM ANHYDROUS
ANHYDROUS->SOLVATE
Related Record Type Details
Structure of N-CARBAMOYL-N-(((5-(4-NITROPHENYL)FURAN-2-YL)METHYLENE)AMINO)GLYCINE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of 1,2-BIS((5-(4-NITROPHENYL)FURAN-2-YL)METHYLENE)HYDRAZINE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of 5-(4-NITROPHENYL)-2-FURALDEHYDE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
Structure of DANTROLENE
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