Interaction between phencyclidine and its pyrolysis product, 1-phenylcyclohexene.
The interaction between phencyclidine (PCP) and its pyrolysis product, 1-phenylcyclohexene (PC), at metabolic level was evaluated in Swiss male mice (21-24 g). PC (1.1, 2.2 and 4.4 mmol/kg/day for 4 days, IP, in corn oil) treatment to mice induced the in vitro metabolism (p less than 0.05) of amidopyrine (17%), aniline (12%), phenacetin (62-100%), pentobarbital (20-26%), PCP (25-80%) and benzo[a]pyrene (81-147%) in the 9000 g liver fraction and the hepatic microsomal contents of cytochrome P-450 (18-42%). The induction of the mixed function oxygenase (MFO) system was consistent with the decreases in the concentrations of IP administered pentobarbital (0.27 mmol/kg, in saline) and PCP (16.4, 32.8 and 65.6 mumol/kg, in saline) in the serum, brain, liver and kidneys of PC pretreated mice. At 1 hr after the above doses of PC, the in vitro metabolism of amidopyrine, aniline, or phenacetin was not inhibited. However, the biotransformation of benzo[a]pyrene was inhibited by 33 to 45%. Though PC after a single dose did not alter the tissue concentrations of PCP, it increased the pentobarbital concentrations in the tissues studied (p less than 0.05). These results indicate that PC has a potential to induce the MFO system after the 4-day treatment. This property of PC plays an important role in the reduction of the action of PCP by enhancing its metabolism, thereby decreasing its tissue levels.
Chaturvedi
A K
AK
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo 58105.
Kuntz
D J
DJ
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D003510:Cyclohexanes / Q000494:pharmacology*; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D007700:Kinetics; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D010424:Pentobarbital / Q000378:metabolism; D010622:Phencyclidine / Q000378:metabolism / Q000494:pharmacology*; D012016:Reference Values
D003510:Cyclohexanes; C034672:1-phenylcyclohex-1-ene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D000815:Aniline Hydroxylase; D001579:Benzopyrene Hydroxylase; D019388:Cytochrome P-450 CYP1A2; D000633:Aminopyrine N-Demethylase; D010424:Pentobarbital; D010622:Phencyclidine