Methohexital

Methohexital

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
Pregnancy category	B (USA)
Routes of administration	Intravenous, rectal
Legal status
Legal status	AU: S4 (Prescription only) US: Schedule IV
Pharmacokinetic data
Bioavailability	I.V. ~100% Rectal ~17%
Metabolism	Hepatic
Biological half-life	5.6 ± 2.7 minutes
Excretion	?
Identifiers
CAS Number	151-83-7 Y
ATC code	N01AF01 (WHO) N05CA15 (WHO)
PubChem	CID 9034
IUPHAR/BPS	7233
DrugBank	DB00474 Y
ChemSpider	8683 Y
UNII	E5B8ND5IPE Y
KEGG	D04985 Y
ChEBI	CHEBI:102216 Y
ChEMBL	CHEMBL7413 Y
Chemical data
Formula	C14H18N2O3
Molar mass	262.304
3D model (Jmol)	Interactive image
SMILES O=C1N(C(=O)NC(=O)C1(C\C=C)C(C#CCC)C)C
InChI 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) Y Key:NZXKDOXHBHYTKP-UHFFFAOYSA-N Y
(verify)

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 GABA_A receptors. 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. 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 minutes 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.

External links

• RxList.com - Methohexital
• Drugs.com - Methohexital Sodium
• DrugLib.com - Brevital (Methohexital Sodium)