Synthesis and pharmacological activity of thiohexital enantiomers.
(S)-(+)- and (R)-(-)-5-Allyl-5-(1-methyl-2-pentynyl)-2-thiobarbituric acid (1, thiohexital) were prepared. The anesthetic activity (loss of righting reflex) and acute toxicity of the optically pure enantiomers of 1 were compared to the racemic isomer in mice. The S(+) isomer was found to be more potent as an anesthetic agent than the R(-) or RS(+/-) isomers. The therapeutic index was 2.5, 2.4, and 3.2 for the RS(+/-), R(-), and S(+) isomers, respectively. There were no significant differences in onset and duration of anesthesia when administered at the respective AD50 values. The prominent side effect is tremor, which is less for the S(+) isomer than for the R(-) or RS(+/-) isomers.
D000777:Anesthetics / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013840:Thiamylal / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D000777:Anesthetics; D013840:Thiamylal; C033298:thiohexital