Identification

Name
Methohexital
Accession Number
DB00474  (APRD00058)
Type
Small Molecule
Groups
Approved
Description

An intravenous anesthetic with a short duration of action that may be used for induction of anesthesia. [PubChem]

Structure
Thumb
Synonyms
  • (+-)-5-Allyl-1-methyl-5-(1-methyl-2-pentynyl)barbituric acid
  • 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
  • alpha-DL-1-Methyl-5-allyl-5-(1'-methylpentyn-2-yl)barbituric acid
  • Methohexital
  • Methohexitalum
  • Methohexitone
  • Metohexital
Product Ingredients
IngredientUNIICASInChI Key
Methohexital sodium60200PNZ7Q309-36-4KDXZREBVGAGZHS-UHFFFAOYSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Brevital SodiumInjection, powder, lyophilized, for solution500 mg/5mLIntramuscular; Intravenous; RectalPhysicians Total Care, Inc.1960-06-272003-06-30Us
Brevital SodiumInjection, powder, lyophilized, for solution200 mg/1Intramuscular; Intravenous; RectalJHP Pharmaceuticals LLC2013-03-202013-03-14Us
Brevital SodiumInjection2.5 g/1Intramuscular; RectalMonarch Pharmaceuticals, Inc.2006-10-102006-11-22Us
Brevital SodiumInjection, powder, lyophilized, for solution2.5 g/1Intramuscular; Intravenous; RectalPar Pharmaceutical, Inc.2007-11-01Not applicableUs
Brevital SodiumInjection, powder, lyophilized, for solution500 mg/1Intramuscular; Intravenous; RectalA S Medication Solutions2007-11-012013-06-07Us
Brevital SodiumInjection500 mg/1Intramuscular; RectalMonarch Pharmaceuticals, Inc.2006-10-102006-11-22Us
Brevital SodiumInjection, powder, lyophilized, for solution500 mg/1Intramuscular; Intravenous; RectalPar Pharmaceutical, Inc.2007-11-01Not applicableUs
Brietal Sodium Ampoule 660Powder, for solution500 mgIntravenousEli Lilly & Co. Ltd.1960-12-312000-08-03Canada
International/Other Brands
Brevital / Brietal
Categories
UNII
E5B8ND5IPE
CAS number
151-83-7
Weight
Average: 262.3043
Monoisotopic: 262.131742452
Chemical Formula
C14H18N2O3
InChI Key
NZXKDOXHBHYTKP-UHFFFAOYSA-N
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)
IUPAC Name
5-(hex-3-yn-2-yl)-1-methyl-5-(prop-2-en-1-yl)-1,3-diazinane-2,4,6-trione
SMILES
CCC#CC(C)C1(CC=C)C(=O)NC(=O)N(C)C1=O

Pharmacology

Indication

Methohexital is indicated for use as an intravenous anaesthetic. It has also been commonly used to induce deep sedation.

Associated Therapies
Pharmacodynamics

Methohexital, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation.

Mechanism of action

Methohexital binds at a distinct binding site associated with a Cl- ionopore at the GABAA receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

TargetActionsOrganism
AGamma-aminobutyric acid receptor subunit alpha-1
antagonist
Human
Absorption

The absolute bioavailability following rectal administration of methohexital is 17%.

Volume of distribution
Not Available
Protein binding

73%

Metabolism

Metabolism occurs in the liver through demethylation and oxidation. Side-chain oxidation is the most important biotransformation involved in termination of biologic activity.

Route of elimination

Excretion occurs via the kidneys through glomerular filtration.

Half life

5.6 ± 2.7 minutes

Clearance
Not Available
Toxicity

The onset of toxicity following an overdose of intravenously administered methohexital will be within seconds of the infusion. If methohexital is administered rectally or is ingested, the onset of toxicity may be delayed. The manifestations of an ultrashort-acting barbiturate in overdose include central nervous system depression, respiratory depression, hypotension, loss of peripheral vascular resistance, and muscular hyperactivity ranging from twitching to convulsive-like movements. Other findings may include convulsions and allergic reactions. Following massive exposure to any barbiturate, pulmonary edema, circulatory collapse with loss of peripheral vascular tone, and cardiac arrest may occur.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Methohexital.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Methohexital.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Methohexital is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be decreased when it is combined with Methohexital.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Methohexital is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Methohexital is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Methohexital.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Methohexital is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Methohexital is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanineThe serum concentration of 6-O-benzylguanine can be decreased when it is combined with Methohexital.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014617
KEGG Drug
D04985
KEGG Compound
C07844
PubChem Compound
9034
PubChem Substance
46507954
ChemSpider
8683
ChEBI
102216
ChEMBL
CHEMBL7413
Therapeutic Targets Database
DAP000677
PharmGKB
PA164784030
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Methohexital
ATC Codes
N01AF01 — MethohexitalN05CB01 — Combinations of barbituratesN05CA15 — Methohexital
FDA label
Download (184 KB)
MSDS
Download (46.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentDepression1
4CompletedTreatmentDepression, Bipolar / Unipolar Depression1
Not AvailableCompletedTreatmentDepression1
Not AvailableCompletedTreatmentMajor Depressive Disorder (MDD)1
Not AvailableCompletedTreatmentOrientation / Post-anesthesia Recovery1
Not AvailableRecruitingTreatmentAnaesthesia therapy / Arterial Hypotension1
Not AvailableTerminatedTreatmentDepression, Bipolar / Major Depressive Disorder (MDD)1

Pharmacoeconomics

Manufacturers
  • Jhp pharmaceuticals llc
Packagers
  • JHP Pharmaceuticals LLC
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
InjectionIntramuscular; Rectal2.5 g/1
InjectionIntramuscular; Rectal500 mg/1
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous; Rectal2.5 g/1
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous; Rectal200 mg/1
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous; Rectal500 mg/5mL
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous; Rectal500 mg/1
Powder, for solutionIntravenous500 mg
Prices
Unit descriptionCostUnit
Brevital sodium 2.5 gm vial221.2USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP1.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0524 mg/mLALOGPS
logP2.43ALOGPS
logP2.29ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)8.73ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area66.48 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity71.51 m3·mol-1ChemAxon
Polarizability27.4 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9143
Blood Brain Barrier+0.982
Caco-2 permeable+0.5
P-glycoprotein substrateNon-substrate0.6307
P-glycoprotein inhibitor IInhibitor0.5661
P-glycoprotein inhibitor IINon-inhibitor0.9294
Renal organic cation transporterNon-inhibitor0.9297
CYP450 2C9 substrateNon-substrate0.823
CYP450 2D6 substrateNon-substrate0.8823
CYP450 3A4 substrateNon-substrate0.6454
CYP450 1A2 substrateNon-inhibitor0.8001
CYP450 2C9 inhibitorNon-inhibitor0.8179
CYP450 2D6 inhibitorNon-inhibitor0.9099
CYP450 2C19 inhibitorNon-inhibitor0.7836
CYP450 3A4 inhibitorNon-inhibitor0.8501
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.954
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8264
BiodegradationNot ready biodegradable0.9737
Rat acute toxicity2.9098 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.978
hERG inhibition (predictor II)Non-inhibitor0.9697
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (12.5 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0fbc-9520000000-5141cdceea7f6d5013b0
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as barbituric acid derivatives. These are compounds containing a perhydropyrimidine ring substituted at C-2, -4 and -6 by oxo groups.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrimidines and pyrimidine derivatives
Direct Parent
Barbituric acid derivatives
Alternative Parents
N-acyl ureas / Diazinanes / Dicarboximides / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Barbiturate / N-acyl urea / Ureide / 1,3-diazinane / Dicarboximide / Urea / Carbonic acid derivative / Carboxylic acid derivative / Azacycle / Organic nitrogen compound
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
barbiturates, acetylenic compound (CHEBI:102216)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
Gene Name
GABRA1
Uniprot ID
P14867
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-1
Molecular Weight
51801.395 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Koltchine VV, Ye Q, Finn SE, Harrison NL: Chimeric GABAA/glycine receptors: expression and barbiturate pharmacology. Neuropharmacology. 1996;35(9-10):1445-56. [PubMed:9014160]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Ouellette R. and Joyce J. (2011). Pharmacology for Nurse Anesthesiology. Jones and Bartlett Learning, LLC. [ISBN:978-0-7637-8607-6]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:40