Isotopic effect study of propofol deuteration on the metabolism, activity, and toxicity of the anesthetic.
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.
Helfenbein
J
J
ORPHACHEM, Rue Montalembert, BP 184, 63005 Clermont-Ferrand, France. helfenbein@inserm484.u-clermont1.fr
Lartigue
C
C
Noirault
E
E
Azim
E
E
Legailliard
J
J
Galmier
M J
MJ
Madelmont
J C
JC
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
D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D003903:Deuterium; D015742:Propofol