Methohexital

Routes of
administrationIntravenous, rectalDrug classBarbiturateATC codeLegal statusLegal status Pharmacokinetic dataBioavailabilityI.V. ~100%
Rectal ~17%MetabolismLiverElimination half-life5.6 ± 2.7 minutesExcretionexcreted in fecesIdentifiersCAS NumberPubChem CIDIUPHAR/BPSDrugBankChemSpiderUNIIKEGGChEBIChEMBLCompTox Dashboard (EPA)ECHA InfoCard100.005.272 Chemical and physical dataFormulaC₁₄H₁₈N₂O₃Molar mass262.309 g·mol⁻¹3D model (JSmol)  (verify)

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.^[2] 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.^[3] 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.^[1] 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.^[1] 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).^[4] 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.^[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.

References

External links

• "Methohexital". Drug Information Portal. U.S. National Library of Medicine.
• "Methohexital sodium". Drug Information Portal. U.S. National Library of Medicine.