Details of the Drug

General Information of Drug (ID: DM7YMIT)

• Drug Name: Methohexital
• Synonyms: Brevital; Brietal; Enallynymall; Enallynymalum; Methodrexitone; Methohexitalum; Methohexitone; Metoesital; Metohexital; Metoesital [DCIT]; Brevital (TN); Methohexital, Monosodium Salt; Methohexitalum [INN-Latin]; Metohexital [INN-Spanish]; Methohexital (USP/INN); Alpha-DL-1-Methyl-5-allyl-5-(1'-methylpentyn-2-yl)barbituricacid; (+-)-5-Allyl-1-methyl-5-(1-methyl-2-pentynyl)barbituric acid; 1-methyl-5-(1-methylpent-2-yn-1-yl)-5-(prop-2-en-1-yl)pyrimidine-2,4,6(1H,3H,5H)-trione; 1-methyl-5-(1-methylpent-2-yn-1-yl)-5-prop-2-en-1-ylpyrimidine-2,4,6(1H,3H,5H)-trione; 5-Allyl-1-methyl-5-(1-methyl-2-pentynyl)-2,4,6(1H,3H,5H)-pyrimidinetrione; 5-Allyl-1-methyl-5-(1-methyl-pent-2-ynyl)-pyrimidine-2,4,6-trione; 5-Allyl-5-(3-hexyn-2-yl)-1-methylbarbituric acid; 5-hex-3-yn-2-yl-1-methyl-5-prop-2-enyl-1,3-diazinane-2,4,6-trione

Indication

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[1]

• Therapeutic Class: Anesthetics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 262.3
  Logarithm of the Partition Coefficient (xlogp); 2.3
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
  Bioavailability: The bioavailability of drug is 17% []
  Clearance: The drug present in the plasma can be removed from the body at the rate of 12 mL/min/kg [3]
  Elimination: 0.5% 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 5.6 +/- 2.7 minutes [3]
  Metabolism: The drug is metabolized via the liver []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 7.62453 micromolar/kg/day [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.27% [3]
  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 1.1 L/kg [3]
  Water Solubility: The ability of drug to dissolve in water is measured as 100 mg/mL [2]
• Chemical Identifiers:
  Formula: C14H18N2O3
  IUPAC Name: 5-hex-3-yn-2-yl-1-methyl-5-prop-2-enyl-1,3-diazinane-2,4,6-trione
  Canonical SMILES: CCC#CC(C)C1(C(=O)NC(=O)N(C1=O)C)CC=C
  InChI: InChI=1S/C14H18N2O3/c1-5-7-8-10(3)14(9-6-2)11(17)15-13(19)16(4)12(14)18/h6,10H,2,5,9H2,1,3-4H3,(H,15,17,19)
  InChIKey: NZXKDOXHBHYTKP-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 9034
  ChEBI ID: CHEBI:102216
  CAS Number: 151-83-7
  DrugBank ID: DB00474
  TTD ID: D0S8TD

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
GABA(A) receptor alpha-1 (GABRA1)	TT1MPAY	GBRA1_HUMAN	Antagonist	[5]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Methohexital

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Propofol	DMB4OLE	Moderate	Additive cardiorespiratory depression effects by the combination of Methohexital and Propofol.	Corneal disease [9A76-9A78]	[6]

Coadministration of a Drug Treating the Disease Different from Methohexital (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Mitotane	DMU1GX0	Minor	Increased metabolism of Methohexital caused by Mitotane mediated induction of CYP450 enzyme.	Adrenal cancer [2D11]	[7]
Nifedipine	DMSVOZT	Moderate	Increased metabolism of Methohexital caused by Nifedipine mediated induction of CYP450 enzyme.	Angina pectoris [BA40]	[8]
Aminophylline	DML2NIB	Moderate	Increased metabolism of Methohexital caused by Aminophylline mediated induction of CYP450 enzyme.	Asthma [CA23]	[9]
Ethanol	DMDRQZU	Major	Additive CNS depression effects by the combination of Methohexital and Ethanol.	Cystitis [GC00]	[10]
Paroxetine	DM5PVQE	Minor	Increased metabolism of Methohexital caused by Paroxetine mediated induction of CYP450 enzyme.	Depression [6A70-6A7Z]	[11]
Fosphenytoin	DMOX3LB	Moderate	Increased metabolism of Methohexital caused by Fosphenytoin mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[12]
Nicardipine	DMCDYW7	Moderate	Increased metabolism of Methohexital caused by Nicardipine mediated induction of CYP450 enzyme.	Essential hypertension [BA00]	[8]
Cimetidine	DMH61ZB	Minor	Altered absorption of Methohexital caused by Cimetidine.	Gastro-oesophageal reflux disease [DA22]	[13]
Levamlodipine	DM92S6N	Moderate	Increased metabolism of Methohexital caused by Levamlodipine mediated induction of CYP450 enzyme.	Hypertension [BA00-BA04]	[8]
Verapamil	DMA7PEW	Moderate	Increased metabolism of Methohexital caused by Verapamil mediated induction of CYP450 enzyme.	Hypertension [BA00-BA04]	[14]
Biperiden	DME78OA	Moderate	Additive CNS depression effects by the combination of Methohexital and Biperiden.	Parkinsonism [8A00]	[15]
Fenoprofen	DML5VQ0	Minor	Increased metabolism of Methohexital caused by Fenoprofen mediated induction of CYP450 enzyme.	Rheumatoid arthritis [FA20]	[16]
LEE011	DMMX75K	Moderate	Increased metabolism of Methohexital caused by LEE011 mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[17]
Propafenone	DMPIBJK	Minor	Increased metabolism of Methohexital caused by Propafenone.	Ventricular tachyarrhythmia [BC71]	[18]

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: 7233).
• [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] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [6] Gill SS, Wright EM, Reilly CS "Pharmacokinetic interaction of propofol and fentanyl: single bolus injection study." Br J Anaesth 65 (1990): 760-5. [PMID: 2265045]
• [7] Product Information. Lysodren (mitotane). Bristol-Myers Squibb, Princeton, NJ.
• [8] Hamann SR, Blouin RA, Chang SL, et al "Effects of hemodynamic changes on the elimination kinetics of verapamil and nifedipine." J Pharmacol Exp Ther 231 (1984): 301-5. [PMID: 6491984]
• [9] Bukowskyj M, Nakatsu K, Munt PW "Theophylline reassessed." Ann Intern Med 101 (1984): 63-73. [PMID: 6145380]
• [10] Gupta RC, Kofoed J "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J 94 (1966): 863-5. [PMID: 5929537]
• [11] Product Information. Paxil (paroxetine). GlaxoSmithKline, Research Triangle Park, NC.
• [12] Kuranari M, Tatsukawa H, Seike M, et al. "Effect of phenytoin on phenobarbital pharmacokinetics in a patient with epilepsy." Ann Pharmacother 29 (1995): 83-4. [PMID: 7711354]
• [13] Somogyi A, Thielscher S, Gugler R "Influence of phenobarbital treatment on cimetidine kinetics." Eur J Clin Pharmacol 19 (1981): 343-7. [PMID: 7238562]
• [14] Rutledge DR, Pieper JA, Mirvis DM "Effects of chronic phenobarbital on verapamil dispostion in humans." J Pharmacol Exp Ther 246 (1988): 7-13. [PMID: 3392664]
• [15] Product Information. Artane (trihexyphenidyl). Lederle Laboratories, Wayne, NJ.
• [16] Helleberg L, Rubin A, Wolen RL, et al "A pharmacokinetic interaction in man between phenobarbitone and fenoprofen, a new anti-inflammatory agent." Br J Clin Pharmacol 1 (1974): 371-4. [PMID: 22454912]
• [17] Cerner Multum, Inc. "Australian Product Information.".
• [18] Sams RA, Muir WW. Effects of phenobarbital on thiopental pharmacokinetics in greyhounds. Am J Vet Res. 1988;49(2):245-249. [PMID: 3348533]