Abstract
Phencyclidine (PCP), a psychotomimetic drug with anticonvulsant and neuroprotective properties interacts with several central nervous system (CNS) macromolecules. These include cholinergic receptors, potassium channels, biogenic amine reuptake systems, the N- methyl- d-aspartate (NMDA) excitatory amino acid receptor, and sigma binding sites. The good correlation between the affinity of arylcycloalkylamines for high affinity PCP binding sites and their ED 50 values for inhibition of [ 3H]dopamine uptake supports the notion that a PCP binding site associated with the transporter for the biogenic amines should be detectable in ligand binding studies. This article reviews data primarily from the author's laboratory, which shows that the PCP analog, [ 3H]1-[1-(2-thienyl)cyclohexyl]piperidine, binds to a second site, not associated with the NMDA receptor/ionophore complex, called PCP site 2. The ligand-selectivity of this binding site and the evidence that it is associated with the biogenic amine transporters are reviewed.
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