AUTHOR OF THIS BLOG

DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER
Jan 182015
 

Skeletal formula

 

Ball-and-stick model

Methohexital or methohexitone, (marketed under the brand name Brevital) is a drug which is a barbiturate derivative. It is classified as short-acting, and has a rapid onset of action. It is similar in its effects to sodium thiopental, a drug with which it competed in the market for anaesthetics.

 

Pharmacology

Methohexital binds to a distinct site which is associated with Cl ionophores at GABAA receptors.[1] This increases the length of time which the Cl ionopores are open, thus causing an inhibitory effect.

Metabolism of methohexital is primarily hepatic (i.e., taking place in the liver) via demethylation and oxidation.Side-chain oxidation is the primary means of metabolism involved in the termination of the drug’s biological activity.

Protein binding is approximately 73% for methohexital.

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.[citation needed] 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 a electroconvulsive therapy (ECT). And rapid recovery rate with consciousness being gained within three to seven minutes after induction and full recovery within 30 minuntes is a major advantage over other ECT barbiturates (Schulgasser and Borowitz 1963).

Synthesis

Methohexital, 5-allyl-1-methyl-5-(1-methyl-2-pentinyl barbituric acid, is synthesized in the classic manner of making barbituric acid derivatives, in particular by the reaction of malonic ester derivatives with derivatives of urea.

Methohexital synthesis: W.J. Doran, U.S. Patent 2,872,448 (1959).

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 desired methohexital.

Methohexital
Skeletal formula
Ball-and-stick model
Systematic (IUPAC) name
5-hex-3-yn-2-yl-1- methyl-5-prop-2-enyl-1, 3-diazinane-2,4,6-trione
Clinical data
AHFS/Drugs.com Consumer Drug Information
Legal status
Routes Intravenous, rectal
Pharmacokinetic data
Bioavailability I.V. ~100%
Rectal ~17%
Metabolism Hepatic
Half-life 5.6 ± 2.7 minutes
Excretion ?
Identifiers
CAS number 151-83-7 Yes
ATC code N01AF01 N05CA15
PubChem CID 9034
DrugBank DB00474
ChemSpider 8683 Yes
UNII E5B8ND5IPE Yes
KEGG D04985 Yes
ChEBI CHEBI:102216 Yes
ChEMBL CHEMBL7413 Yes
Chemical data
Formula C14H18N2O3 
Molecular mass 262.304

 

References

  1. Katzung, Bertram G., Basic and Clinical Pharmacology, 10th ed., p. 406-407

[1]

External links

 

Share

Sorry, the comment form is closed at this time.

Follow

Get every new post on this blog delivered to your Inbox.

Join other followers: