Effects of inducers and/or inhibitors on metabolism of lysergic acid diethylamide in rat liver microsomes
Takako Inoue, Tetsukichi Niwaguchi, Toshiro Murata
Xenobiotica 1980 DOI: 10.3109/00498258009033825 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat liver microsomes |
| Intervention | SKF 525-A |
| Topics | LSD |
| Citations | 3 |
| Key findings | LSD metabolism in rat liver microsomes is catalyzed by at least three separate enzyme systems, and 13-hydroxylation in microsomes from 3-methylcholanthrene-treated rats involves an unusual cytochrome P-448. |
Abstract
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.