PT  - JOURNAL ARTICLE
AU  - M K Hoag
AU  - A J Trevor
AU  - Y Asscher
AU  - J Weissman
AU  - N Castagnoli, Jr
TI  - Metabolism-dependent inactivation of liver microsomal enzymes by phencyclidine.
DP  - 1984 May 01
TA  - Drug Metabolism and Disposition
PG  - 371--375
VI  - 12
IP  - 3
4099  - http://dmd.aspetjournals.org/content/12/3/371.short
4100  - http://dmd.aspetjournals.org/content/12/3/371.full
SO  - Drug Metab Dispos1984 May 01; 12
AB  - Incubation of phencyclidine (PCP) with rabbit liver microsomes resulted in NADPH-dependent loss of N-demethylase activity accompanied by reduction in microsomal cytochrome P-450 content. This effect was concentration-dependent, exhibited pseudo-first order kinetics, and was irreversible, thus exhibiting characteristics of "suicide substrate" inhibition. Cyanide ions at low concentrations, which have been used to trap the iminium intermediate of PCP metabolism as its cyano adduct, antagonized the inhibition of N-demethylase by PCP. PCP iminium ions were effective inhibitors of microsomal enzyme activity but required NADPH. These results support our suggestions that iminium ion formation is an intermediary step in the bioactivation of PCP leading to reactive electrophilic species.