Details of the Drug

General Information of Drug (ID: DM1D8XY)

Drug Name
Dantrolene
Synonyms
Dantrium; Dantroleno; Dantrolenum; DANTROLENE SODIUM; Dantrium Intravenous; Dantrium (TN); Dantrolen (TN); Dantroleno [INN-Spanish]; Dantrolenum [INN-Latin]; F-368; Dantrolene (USAN/INN); Dantrolene [USAN:BAN:INN]; 1-(((5-(4-Nitrophenyl)-2-furanyl)methylene)amino)-2,4-imidazolidinedione; 1-((5-(p-Nitrophenyl)furfurylidene)amino)hydantoin; 1-({(1E)-[5-(4-nitrophenyl)furan-2-yl]methylidene}amino)imidazolidine-2,4-dione; 1-({[5-(4-nitrophenyl)furan-2-yl]methylidene}amino)imidazolidine-2,4-dione; 1-[(E)-[5-(4-nitrophenyl)furan-2-yl]methylideneamino]imidazolidine-2,4-dione
Indication
Disease Entry ICD 11 Status REF
Hyperthermia MG26 Approved [1]
Therapeutic Class
Muscle Relaxants
Affected Organisms
Humans and other mammals
ATC Code
M03CA01: Dantrolene
M03CA: Dantrolene and derivatives
M03C: MUSCLE RELAXANTS, DIRECTLY ACTING AGENTS
M03: MUSCLE RELAXANTS
M: MUSCULO-SKELETAL SYSTEM
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 314.25
Logarithm of the Partition Coefficient (xlogp) 1.7
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 6
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
Bioavailability
The bioavailability of drug is 70% []
Clearance
The drug present in the plasma can be removed from the body at the rate of 0.43 mL/min/kg [3]
Elimination
5% of drug is excreted from urine in the unchanged form [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 4 - 8 hours [3]
Metabolism
The drug is metabolized via the hepatic []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 21.22449 micromolar/kg/day [4]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.37 L/kg [3]
Water Solubility
The ability of drug to dissolve in water is measured as 2 mg/mL [2]
Chemical Identifiers
Formula
C14H10N4O5
IUPAC Name
1-[(E)-[5-(4-nitrophenyl)furan-2-yl]methylideneamino]imidazolidine-2,4-dione
Canonical SMILES
C1C(=O)NC(=O)N1/N=C/C2=CC=C(O2)C3=CC=C(C=C3)[N+](=O)[O-]
InChI
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+
InChIKey
OZOMQRBLCMDCEG-VIZOYTHASA-N
Cross-matching ID
PubChem CID
6914273
CAS Number
7261-97-4
UNII
F64QU97QCR
DrugBank ID
DB01219
TTD ID
D0I8DD
INTEDE ID
DR0411
ACDINA ID
D00166
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Ryanodine receptor (RYR) TT9YXM1 NOUNIPROTAC Modulator [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [6]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Gene/Protein Processing [7]
Insulin-like growth factor I (IGF1) OTIIZR61 IGF1_HUMAN Protein Interaction/Cellular Processes [8]
Insulin-like growth factor II (IGF2) OTJ4O6MW IGF2_HUMAN Protein Interaction/Cellular Processes [8]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Gene/Protein Processing [9]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Dantrolene (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Increased risk of hepatotoxicity by the combination of Dantrolene and Remdesivir. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [10]
Oliceridine DM6MDCF Major Additive CNS depression effects by the combination of Dantrolene and Oliceridine. Acute pain [MG31] [11]
Bedaquiline DM3906J Moderate Increased risk of hepatotoxicity by the combination of Dantrolene and Bedaquiline. Antimicrobial drug resistance [MG50-MG52] [12]
Pexidartinib DMS2J0Z Major Increased risk of hepatotoxicity by the combination of Dantrolene and Pexidartinib. Bone/articular cartilage neoplasm [2F7B] [13]
Esterified estrogens DM9KZDO Major Increased risk of hepatotoxicity by the combination of Dantrolene and Esterified estrogens. Breast cancer [2C60-2C6Y] [14]
Quinestrol DMJ6H1Z Major Increased risk of hepatotoxicity by the combination of Dantrolene and Quinestrol. Breast cancer [2C60-2C6Y] [14]
Dihydrocodeine DMB0FWL Major Additive CNS depression effects by the combination of Dantrolene and Dihydrocodeine. Chronic pain [MG30] [15]
Mestranol DMG3F94 Major Increased risk of hepatotoxicity by the combination of Dantrolene and Mestranol. Contraceptive management [QA21] [16]
Esketamine DMVU687 Moderate Additive CNS depression effects by the combination of Dantrolene and Esketamine. Depression [6A70-6A7Z] [10]
[3H]estrone-3-sulphate DMGPF0N Major Increased risk of hepatotoxicity by the combination of Dantrolene and [3H]estrone-3-sulphate. Discovery agent [N.A.] [16]
Cannabidiol DM0659E Moderate Increased risk of hepatotoxicity by the combination of Dantrolene and Cannabidiol. Epileptic encephalopathy [8A62] [17]
Brentuximab vedotin DMWLC57 Moderate Increased risk of hepatotoxicity by the combination of Dantrolene and Brentuximab vedotin. Hodgkin lymphoma [2B30] [18]
Mipomersen DMGSRN1 Major Increased risk of hepatotoxicity by the combination of Dantrolene and Mipomersen. Hyper-lipoproteinaemia [5C80] [19]
Teriflunomide DMQ2FKJ Major Increased risk of hepatotoxicity by the combination of Dantrolene and Teriflunomide. Hyper-lipoproteinaemia [5C80] [20]
BMS-201038 DMQTAGO Major Increased risk of hepatotoxicity by the combination of Dantrolene and BMS-201038. Hyper-lipoproteinaemia [5C80] [21]
Levamlodipine DM92S6N Moderate Increased risk of hyperkalemia by the combination of Dantrolene and Levamlodipine. Hypertension [BA00-BA04] [10]
Calaspargase pegol DMQZBXI Moderate Increased risk of hepatotoxicity by the combination of Dantrolene and Calaspargase pegol. Malignant haematopoietic neoplasm [2B33] [22]
Idelalisib DM602WT Moderate Increased risk of hepatotoxicity by the combination of Dantrolene and Idelalisib. Mature B-cell leukaemia [2A82] [23]
Allopregnanolone DMNLHAC Moderate Additive CNS depression effects by the combination of Dantrolene and Allopregnanolone. Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z] [24]
Lasmiditan DMXLVDT Moderate Additive CNS depression effects by the combination of Dantrolene and Lasmiditan. Migraine [8A80] [25]
Flibanserin DM70DTN Moderate Additive CNS depression effects by the combination of Dantrolene and Flibanserin. Mood disorder [6A60-6E23] [26]
Levomethadyl Acetate DM06HG5 Major Additive CNS depression effects by the combination of Dantrolene and Levomethadyl Acetate. Opioid use disorder [6C43] [15]
Trabectedin DMG3Y89 Moderate Increased risk of hepatotoxicity by the combination of Dantrolene and Trabectedin. Solid tumour/cancer [2A00-2F9Z] [17]
⏷ Show the Full List of 23 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Allura red AC dye E00338 33258 Colorant
FD&C blue no. 1 E00263 19700 Colorant
Quinoline yellow WS E00309 24671 Colorant
Sunset yellow FCF E00255 17730 Colorant
Carmellose sodium E00625 Not Available Disintegrant
Eisenoxyd E00585 56841934 Colorant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
⏷ Show the Full List of 11 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Dantrolene 100 mg capsule 100 mg Oral Capsule Oral
Dantrolene 25 mg capsule 25 mg Oral Capsule Oral
Dantrolene 50 mg capsule 50 mg Oral Capsule Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4172).
2 BDDCS applied to over 900 drugs
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
6 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
7 Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
8 Insulin-like growth factors (IGF) I and II utilize different calcium signaling pathways in a primary human parathyroid cell culture model. World J Surg. 2006 Mar;30(3):333-45. doi: 10.1007/s00268-005-0339-8.
9 Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
10 Cerner Multum, Inc. "Australian Product Information.".
11 US Food and Drug Administration "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines requires its strongest warning.".
12 Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
13 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
14 Product Information. Dantrium (dantrolene). Procter and Gamble Pharmaceutic, Cincinnati, OH.
15 US Food and Drug Administration "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines requires its strongest warning.".
16 Fuhr U, Maier-Bruggemann A, Blume H, et al. "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther 36 (1998): 126-32. [PMID: 9562227]
17 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
18 Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
19 Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
20 Canadian Pharmacists Association.
21 Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
22 Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
23 Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
24 Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
25 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
26 Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.