Interaction between phencyclidine and its pyrolysis product, 1-phenylcyclohexene

Area of Science:

• Pharmacology
• Toxicology
• Drug Metabolism

Background:

• Phencyclidine (PCP) is a dissociative anesthetic with complex pharmacological effects.
• Pyrolysis of PCP can produce 1-phenylcyclohexene (PC), a related compound.
• Understanding the metabolic interactions between PCP and PC is crucial for assessing their toxicological profiles.

Purpose of the Study:

• To evaluate the metabolic interaction between phencyclidine (PCP) and its pyrolysis product, 1-phenylcyclohexene (PC).
• To investigate the effect of PC on the metabolism of various xenobiotics, including PCP, in mice.

Main Methods:

• Swiss male mice were treated with PC (1.1, 2.2, and 4.4 mmol/kg/day for 4 days).
• In vitro metabolism assays were performed on liver fractions and hepatic microsomes.
• Concentrations of pentobarbital and PCP in serum, brain, liver, and kidneys were measured after PC pretreatment.

Main Results:

• PC treatment significantly induced the in vitro metabolism of amidopyrine, aniline, phenacetin, pentobarbital, PCP, and benzo[a]pyrene.
• PC pretreatment led to decreased serum and tissue concentrations of pentobarbital and PCP.
• PC also induced cytochrome P-450 content and the mixed-function oxygenase (MFO) system.

Conclusions:

• PC acts as an inducer of the mixed-function oxygenase (MFO) system following repeated exposure.
• This induction enhances the metabolism of PCP, leading to reduced tissue levels and potentially mitigating its pharmacological effects.
• PC's metabolic induction properties are significant in understanding its interaction with PCP.