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

Methohexital
Skeletal formula
Ball-and-stick model
Clinical data
Trade namesBrevital Sodium
Other namesMethohexitone
AHFS/Drugs.comConsumer Drug Information
License data
Routes of
administration		Intravenous, rectal
Drug classBarbiturate
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityI.V. ~100%
Rectal ~17%
MetabolismLiver
Elimination half-life5.6 ± 2.7 minutes
Excretionexcreted in feces
Identifiers
  • 5-Hex-3-yn-2-yl-1-methyl-5-prop-2-enyl-1,3-diazinane-2,4,6-trione
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)
  • O=C1N(C(=O)NC(=O)C1(C\C=C)C(C#CCC)C)C
  • 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) checkY
  • Key:NZXKDOXHBHYTKP-UHFFFAOYSA-N checkY
  (verify)

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.

Methohexital synthesis

References
  1. "Brevital Sodium". DailyMed. 2019-07-24. Retrieved 2019-11-20.
  2. "Methohexital". MeSH.
  3. Katzung BG. Basic and Clinical Pharmacology (10th ed.). pp. 406–407.
  4. Schulgasser H, Borowitz AH (August 1963). "Methohexital anaesthesia in electroconvulsive therapy". South African Medical Journal. 37: 870–1. PMID 14045806.
  5. US 2872448, Doran WJ, "1,5,5-Trisubstituted barbituric acids", issued 3 February 1959, assigned to Eli Lily and Company
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