title: Isotopic effect study of propofol deuteration on the metabolism, activity, and toxicity of the anesthetic.
abstract: The use of isotopic substitution to delay the oxidative metabolism of the anesthetic propofol 1 was studied. The aromatic hydrogens of propofol 1 were replaced by deuterium to produce the mono- and trideuterated derivatives 4 and 5. In vitro metabolic studies on human hepatic microsomes showed no isotopic effect in the para hydroxylation of propofol, and 1, 4, and 5 display similar hypnotic activity and toxicity in mice.
authors.affiliation: ORPHACHEM, Rue Montalembert, BP 184, 63005 Clermont-Ferrand, France. helfenbein@inserm484.u-clermont1.fr
authors.forename: J
authors.initials: J
authors.lastname: Helfenbein
authors.forename: C
authors.initials: C
authors.lastname: Lartigue
authors.forename: E
authors.initials: E
authors.lastname: Noirault
authors.forename: E
authors.initials: E
authors.lastname: Azim
authors.forename: J
authors.initials: J
authors.lastname: Legailliard
authors.forename: M J
authors.initials: MJ
authors.lastname: Galmier
authors.forename: J C
authors.initials: JC
authors.lastname: Madelmont
mesh_terms: D018686:Anesthetics, Intravenous / Q000378:metabolism* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology / Q000633:toxicity; D066298:In Vitro Techniques; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D015742:Propofol / Q000378:metabolism* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D003903:Deuterium; D015742:Propofol