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

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	MOL RATIO 1 MOL RATIO (average)

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

Description

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	Antagonist 2,778		130.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic spasticity 3	Primary		Approved 8,429	DANTRIUM
Malignant hyperthermia 3	Preventing		Approved 8,429	DANTRIUM

C_max

Value	Dose	Co-administered	Analyte	Population
9 μg/mL	2.5 mg/kg single, intravenous		DANTROLENE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
77.7 μg × h/mL	2.5 mg/kg single, intravenous		DANTROLENE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.7 h	100 mg 1 times / day multiple, oral		DANTROLENE blood	Homo sapiens
10.8 h	2.5 mg/kg single, intravenous		DANTROLENE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
25 mg 1 times / day steady, oral (starting)	unhealthy	Disc. AE: Hepatitis, Diarrhea...

Showing 1 to 1 of 1 entries

Previous1Next

AEs

Show entries

AE	Significance	Dose	Population
Diarrhea	Disc. AE	25 mg 1 times / day steady, oral (starting)	unhealthy
Hepatitis	Disc. AE	25 mg 1 times / day steady, oral (starting)	unhealthy

Showing 1 to 2 of 2 entries

Previous1Next

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 599 OAT3 642 MRP4 204	CYP1A1 349 CYP1A2 1,054 CYP3A 191 BCRP 561

Drug as perpetrator

Show entries

Target	Modality	Activity
OAT3 644	inhibitor 3,277	yes [IC50 0.3 uM]
OAT1 603	inhibitor 3,277	yes [IC50 1.89 uM]
MRP4 238	inhibitor 3,277	yes [IC50 5.29 uM]

Showing 1 to 3 of 3 entries

Previous1Next

Drug as victim

Show entries

Target	Modality	Activity
BCRP 561	substrate 3,367	yes
CYP1A1 349	substrate 3,367	yes
CYP1A2 1,054	substrate 3,367	yes
CYP3A 191	substrate 3,367	yes

Showing 1 to 4 of 4 entries

Previous1Next

Sourcing

Sourcing

Show entries

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

Showing 1 to 3 of 3 entries

Previous1Next

PubMed

Show entries

Title	Date	PubMed
Dantrolene hepatitis.	1976 Apr 12	946274
Dantrolene and suxamethonium. The effect of pre-operative dantrolene on the action of suxamethonium.	1979 Feb	375768
Treatment of neuroleptic malignant syndrome with dantrolene.	1982 Jul 3	6123782
Beneficial effects of dantrolene in the treatment of neuroleptic malignant syndrome: a report of two cases.	1983 Apr	6682201
Pneumonitis, pleural effusion and pericarditis following treatment with dantrolene.	1984 May	6736987

Showing 1 to 5 of 41 entries

Previous1 2 3 4 5…9Next

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.