Methohexital

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[1]. It is similar in its effects to sodium thiopental, a drug with which it competed in the market for anaesthetics.

Methohexital
Clinical data
AHFS/Drugs.comConsumer Drug Information
Pregnancy
category
  • B (USA)
Routes of
administration		Intravenous, rectal
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: Schedule IV
Pharmacokinetic data
BioavailabilityI.V. ~100%
Rectal ~17%
MetabolismHepatic
Elimination half-life5.6 ± 2.7 minutes
Excretion?
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.005.272
Chemical and physical data
FormulaC14H18N2O3
Molar mass262.309 g·mol−1
3D model (JSmol)
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Pharmacology

Methohexital binds to a distinct site which is associated with Cl− ionophores at GABAA receptors.[2] 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.[3] 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.[3] 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 make it particularly useful when anesthesia is provided for an electroconvulsive therapy (ECT).[4] And 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.[4]

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.[5] 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


References
  1. "Methohexital". MeSH.
  2. Katzung, Bertram G. Basic and Clinical Pharmacology (10th ed.). p. 406-407.
  3. "BREVITAL SODIUM". DailyMed. 2019-07-24. Retrieved 2019-11-20.
  4. Schulgasser, H; Borowitz, A (1963). "Methohexital anaesthesia in electroconvulsive therapy". South African Medical Journal. 37: 870.
  5. W.J. Doran, U.S. Patent 2,872,448 (1959)


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