DANTROLENE SODIUM

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 Search

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
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 2778		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 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 1974
Malignant hyperthermia 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017443s043s046s048s049lbl.pdf	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 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

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: 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

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: 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

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 599 OAT3 642 MRP4 204	CYP1A1 349 CYP1A2 1054 CYP3A 191 BCRP 561

Drug as perpetrator

Target	Modality	Activity
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/28630284/	yes [IC50 0.3 uM]
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/28630284/	yes [IC50 1.89 uM]
MRP4 238	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/28630284/	yes [IC50 5.29 uM]

Drug as victim

Target	Modality	Activity
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22115838/	yes
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/7902259/	yes
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/7902259/	yes
CYP3A 191	substrate 3367 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
Dantrolene and lymphocytic lymphoma.	1980 Apr	6893628
Treatment of neuroleptic malignant syndrome with dantrolene.	1982 Jul 3	6123782
Hyperkalemia and cardiovascular collapse after verapamil and dantrolene administration in swine.	1984 May	6711841
[Cardiac failure caused by an overdose of dantrolene].	1986	3826797
Prevention of amphotericin B-induced rigors by dantrolene.	1986 Aug	3729640
Sudden bilateral sensorineural hearing loss during treatment with dantrolene sodium (dantrium).	1988 Jan	3343565
[Successful treatment of levodopa-induced neuroleptic malignant syndrome (NMS) with disseminated intravascular coagulation (DIC) in a patient with Parkinson's disease].	1991 Jan	2044308
Management of neuroleptic malignant syndrome--a series of eight cases.	1993 Feb	8101521
[A case of malignant syndrome triggered by the use of haloperidol and chrorpromazine].	1997 Apr	9128030
Neuronal apoptosis induced by pharmacological concentrations of 3-hydroxykynurenine: characterization and protection by dantrolene and Bcl-2 overexpression.	2000 Jul	10854250
Dantrolene inhibition of ryanodine receptor Ca2+ release channels. Molecular mechanism and isoform selectivity.	2001 Apr 27	11278295
Mechanism of the beneficial effects of dantrolene sodium on ethanol-induced acute gastric mucosal injury in rats.	2002 May	12123631
Atypical neuroleptic malignant syndrome caused by clozapine and venlafaxine: early brief treatment with dantrolene.	2004 Jul	15362259
Drug-induced liver injury.	2004 Mar 1	14986274
Carbamazepine toxicity following Oxybutynin and Dantrolene administration: a case report.	2005 Apr	15685264
Non-paracetamol drug-induced fulminant hepatic failure among adults in Scotland.	2005 Feb	15674093
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Insulin-like growth factors (IGF) I and II utilize different calcium signaling pathways in a primary human parathyroid cell culture model.	2006 Mar	16485066
Transitional cell carcinoma in the paediatric population: be aware of unusual aetiologies.	2007 Nov	17924939
Identification of functional type 1 ryanodine receptors in human dendritic cells.	2007 Oct 19	17707769
Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition.	2008 Dec	18493746
Diphenyl ditelluride induces hypophosphorylation of intermediate filaments through modulation of DARPP-32-dependent pathways in cerebral cortex of young rats.	2012 Feb	21863293

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 `Fri Dec 15 15:24:38 GMT 2023` Edited by `admin` on `Fri Dec 15 15:24:38 GMT 2023`
Record UNII	287M0347EV
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DANTROLENE SODIUM

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

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

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