Methohexital

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 Edit this at Wikidata
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)

Methohexital (generic INN), with the trade names Brevital and Bietal, amongst others, is a barbiturate known as a rapid-acting CNS depressant drug rapid onset inducing anesthesia; efficacy rapid onset of action and its short duration of action has drawn resemblance to sodium thiopental. It is similar in its effects to sodium thiopental, a drug it competed with in the market for anesthetics.[citation needed]

Pharmacology

Methohexital binds to a distinct site which is associated with Cl− ionophores at GABAA receptors. This increases the length of time which the Cl− ionopores are open, causing an inhibitory effect. Metabolism of methohexital is primarily hepatic via demethylation and side-chain oxidation.

Indications

Methohexital is primarily used to induce anesthesia, and is generally provided as a sodium salt (e.g., 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 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.

References

  1. 1 2 3 "Brevital Sodium". DailyMed. July 24, 2019. Retrieved November 20, 2019.
  2. ↑ "Methohexital". MeSH.
  3. ↑ Katzung BG. Basic and Clinical Pharmacology (10th ed.). pp. 406–407.
  4. 1 2 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 February 3, 1959, assigned to Eli Lily and Company (U.S. patent 2,872,448)