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Related Experiment Videos

Biotransformation of phencyclidine.

E J Holsztynska, E F Domino

    Drug Metabolism Reviews
    |January 1, 1985
    PubMed
    Summary

    Phencyclidine (PCP) undergoes extensive metabolism in the body, primarily through hydroxylation, producing less active metabolites. Reactive metabolites may contribute to PCP toxicity and cytochrome P-450 inactivation.

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    Area of Science:

    • Pharmacology
    • Toxicology
    • Drug Metabolism

    Background:

    • Phencyclidine (PCP) is extensively metabolized through various routes, representing a major elimination mechanism.
    • PCP metabolites generally exhibit reduced pharmacological activity compared to the parent compound.

    Purpose of the Study:

    • To elucidate the metabolic pathways and identify the metabolites of phencyclidine (PCP).
    • To understand the role of PCP metabolites in its pharmacological action and toxicity.

    Main Methods:

    • In vitro studies using microsomal preparations to identify reactive metabolites.
    • Analysis of metabolic routes including hydroxylation and conjugation.

    Main Results:

    • Primary metabolism involves cytochrome P-450-mediated hydroxylation of alicyclic rings.
    • Formation of polar, open-ring compounds from piperidine ring hydroxylation.
    • Evidence of reactive electrophilic metabolites formed in vitro, potentially causing P450 inactivation and long-term toxicity.

    Conclusions:

    • PCP metabolism is extensive, yielding less active compounds.
    • Reactive metabolites may play a role in PCP-induced toxicity and enzyme inactivation.
    • Metabolism of inhaled PCP follows similar pathways, with limited contribution from PC and its metabolites to acute effects.

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