Chemistry:Methohexital

Short description: Anesthetic and barbiturate-type sedative

Methohexital

Clinical data
Trade names	Brevital Sodium
Other names	Methohexitone
AHFS/Drugs.com	Consumer Drug Information
License data	US DailyMed: Methohexital
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	Intravenous, rectal
Drug class	Barbiturate
ATC code	N01AF01 (WHO) N05CA15 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) US: Schedule IV
Pharmacokinetic data
Bioavailability	I.V. ~100% Rectal ~17%
Metabolism	Liver
Elimination half-life	5.6 ± 2.7 minutes
Excretion	excreted in feces
Identifiers
IUPAC name 5-Hex-3-yn-2-yl-1-methyl-5-prop-2-enyl-1,3-diazinane-2,4,6-trione
CAS Number	151-83-7 Y
PubChem CID	9034
IUPHAR/BPS	7233
DrugBank	DB00474 Y
ChemSpider	8683 Y
UNII	E5B8ND5IPE
KEGG	D04985 Y
ChEBI	CHEBI:102216 Y
ChEMBL	ChEMBL7413 Y
Chemical and physical data
Formula	C14H18N2O3
Molar mass	262.309 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C1N(C(=O)NC(=O)C1(C\C=C)C(C#CCC)C)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) Y Key:NZXKDOXHBHYTKP-UHFFFAOYSA-N Y
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Methohexital or methohexitone (marketed under the brand names Brevital and Brietal) is a drug which is a barbiturate derivative. It is classified as short-acting, and has a rapid onset of action. It is similar in its effects to sodium thiopental, a drug with which it competed in the market for anesthetics.

Pharmacology

Methohexital binds to a distinct site which is associated with Cl⁻ ionophores at GABA_A receptors. This increases the length of time which the Cl⁻ ionopores are open, thus causing an inhibitory effect.

Metabolism of methohexital is primarily hepatic via demethylation and oxidation. Side-chain oxidation is the primary means of metabolism involved in the termination of the drug's biological activity.

Indications

Methohexital is primarily used to induce anesthesia, and is generally provided as a sodium salt (i.e. methohexital sodium). It is only used in hospital or similar settings, under strict supervision. It has been commonly used to induce deep sedation or general anesthesia for surgery and dental procedures. Unlike many other barbiturates, methohexital actually lowers the seizure threshold, a property that makes it particularly useful when anesthesia is provided for an electroconvulsive therapy (ECT). Its rapid recovery rate with consciousness being gained within three to seven minutes after induction and full recovery within 30 minutes is a major advantage over other ECT barbiturates.

Synthesis

Methohexital can be synthesized in the classic manner of making barbituric acid derivatives, in particular by the reaction of malonic ester derivatives with derivatives of urea. The resulting allyl-(1-methyl-2-pentynyl) malonic ester is synthesized by subsequent alkylation of the malonic ester itself, beginning with 2-bromo-3-hexyne, which gives (1-methyl-2-pentynyl)malonic ester, and then by allylbromide. In the final step, reaction of the disubstituted malonic ester with N-methylurea gives methohexital.

Methohexital synthesis

External links

• "Methohexital". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/rn/151-83-7. 
• "Methohexital sodium". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/methohexital%20sodium.