Phencyclidine (PCP) is a psychotomimetic agent that is extensively abused and whose intoxication is a major emergency room problem. The compound has no therapeutic indication in man and is manufactured and sold through illicit channels. As a result, the material is poorly quality controlled so that material sold as PCP can be material synthesized with alternate starting materials. Consequently, an array of phencyclidine derivatives have been sold as """"""""PCP"""""""". The object of this research is to establish the biochemistry of PCP metabolism in terms of pathways, enzymology, and mechanisms so that the changes in metabolism that may occur with structural changes can be predicted. In a more general sense, these questions are being addressed to many nitrogen containing compounds that are drugs of abuse. The study focuses on the metabolism of the heterocyclic ring of PCP because this pathway generates active metabolites and is the dominant pathway of metabolism in man. The objective is to be met in three specific aims: (1) to determine the biochemistry of phenylcyclohexylamine formation; (2) to determine the effect of heterocyclic ring size on metabolism; and (3) to examine heterocyclic ring metabolism in other drugs of abuse such as cocaine and fentanyl. The research utilizes in vitro and in vivo procedures with rats and rabbits, and GC, GCMS, and HPLC techniques for analysis. Stable isotope substituted variants are also used as probes in mechanistic studies.
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