Methohexital

Methohexital
Clinical data
Trade names	Brevital Sodium
AHFS/Drugs.com	Consumer Drug Information
License data	US DailyMed: Methohexital;
Routes of; administration	Intravenous, rectal
ATC code	N01AF01 (WHO) N05CA15 (WHO);
Legal status
Legal status	AU: S4 (Prescription only) ; US: Schedule IV ;
Pharmacokinetic data
Bioavailability	I.V. ~100%; Rectal ~17%
Metabolism	Liver
Elimination half-life	5.6 ± 2.7 minutes
Excretion	excreted in feces
Identifiers
	IUPAC name 5-Hex-3-yn-2-yl-1-methyl-5-prop-2-enyl-1,3-diazinane-2,4,6-trione;
CAS Number	151-83-7 ;
PubChem CID	9034;
IUPHAR/BPS	7233;
DrugBank	DB00474 ;
ChemSpider	8683 ;
UNII	E5B8ND5IPE;
KEGG	D04985 ;
ChEBI	CHEBI:102216 ;
ChEMBL	ChEMBL7413 ;
CompTox Dashboard (EPA)	DTXSID1023287 ;
ECHA InfoCard	100.005.272
Chemical and physical data
Formula	C14H18N2O3
Molar mass	262.309 g·mol−1
3D model (JSmol)	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) ; Key:NZXKDOXHBHYTKP-UHFFFAOYSA-N ;
	(verify)

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.

Pharmacology

Methohexital binds to a distinct site which is associated with Cl⁻ ionophores at GABA_A 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 make it particularly useful when anesthesia is provided for an electroconvulsive therapy (ECT).^[4] 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.^[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

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

External links

"Methohexital". Drug Information Portal. U.S. National Library of Medicine.
"Methohexital sodium". Drug Information Portal. U.S. National Library of Medicine.

[Brevital_Sodium_FDA_label-1] "Brevital Sodium". DailyMed. 2019-07-24. Retrieved 2019-11-20.

[2] "Methohexital". MeSH.

[3] Katzung BG. Basic and Clinical Pharmacology (10th ed.). p. 406-407.

[Schulgasser-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

[1]

[2]

[3]

[4]

[5]