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 GABAA 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.
