Enzymic formation of dehydrogenated and hydroxylated metabolites from lysergic acid diethylamide by rat liver microsomes

Rat liver microsomes metabolize LSD into several products. Two previously reported metabolites, lysergic acid ethylamide and nor-LSD, were found alongside two newly identified ones: lysergic acid ethylvinylamide, formed by dehydrogenation of the side chain, and 13-hydroxy-LSD, a phenol. Pretreatment of rats with phenobarbitone sodium induced formation of lysergic acid ethylamide, lysergic acid ethylvinylamide, and nor-LSD, while 3-methylcholanthrene induced lysergic acid ethylamide, lysergic acid ethylvinylamide, and 13-hydroxy-LSD. Nor-LSD formation was induced only by phenobarbitone, and 13-hydroxy-LSD only by methylcholanthrene.

Study at a glance

Abstract

1. The metabolism of lysergic acid diethylamide (LSD) was studied using rat liver microsomes, and two minor metabolites were obtained in addition to lysergic acid ethylamide and N6-desmethyl-lysergic acid diethylamide (nor-LSD) which were reported previously. 2. One of the metabolites was identified as lysergic acid ethylvinylamide, apparently formed by dehydrogenation of a diethylamide group in the side chain at the 8-position, and the other as the phenol 13-hydroxy-LSD. 3. The formation of both lysergic acid ethylamide and lysergic acid ethylvinylamide was similarly induced by pretreatment of rats with either phenobarbitone sodium or 3-methylcholanthrene, while nor-LSD formation was induced only by phenobarbitone and that of 13-hydroxy-LSD only by methylcholanthrene.