RT Journal Article SR Electronic T1 Metabolism-dependent inactivation of liver microsomal enzymes by phencyclidine. JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 371 OP 375 VO 12 IS 3 A1 M K Hoag A1 A J Trevor A1 Y Asscher A1 J Weissman A1 N Castagnoli, Jr YR 1984 UL http://dmd.aspetjournals.org/content/12/3/371.abstract 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.