Effects of inducers and/or inhibitors on metabolism of lysergic acid diethylamide in rat liver microsomes.
1. When lysergic acid diethylamide (LSD) was incubated with liver microsomes obtained from untreated rats, SKF 525-A inhibited most potently the hydroxylation at the 13-position, moderately inhibited N-demethylation at the 6-position, and least affected the metabolism of the side-chain at the 8 position. Furthermore, an atmosphere of 80% CO and 20% O2 (v/v) caused max. inhibition in N-demethylation, moderate inhibition in 13-hydroxylation, and the minimum in metabolism of the side-chain at the 8-position. These data suggested that the metabolism of LSD is catalysed by three separate enzyme systems. 2. The formation of 13-hydroxy-lysergic acid diethylamide (13-hydroxy-LSD) in liver microsomes obtained from 3-methylcholanthrene-treated rats was not inhibited by CO, although the hydroxylation required NADPH and oxygen. 3. The results of experiments using various inhibitors suggest that the 13-hydroxylation in liver microsomes from 3-methylcholanthrene-treated rats is catalysed by an enzyme system involving an unusual type of cytochrome P-448.
D000818:Animals; D001711:Biotransformation; D002248:Carbon Monoxide / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008238:Lysergic Acid Diethylamide / Q000378:metabolism*; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D010101:Oxygen Consumption; D010634:Phenobarbital / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D051381:Rats
D004791:Enzyme Inhibitors; D009243:NAD; D008748:Methylcholanthrene; D002248:Carbon Monoxide; D008238:Lysergic Acid Diethylamide; D011335:Proadifen; D010634:Phenobarbital