PCP site 2: a high affinity MK-801-insensitive phencyclidine binding site.
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 ED50 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.
Clinical Psychopharmacology Section, NIDA Addiction Research Center, Baltimore, MD 21224.
R B
RB
Rothman
D000818:Animals; D001665:Binding Sites; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002645:Chickens; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D006168:Guinea Pigs; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D009419:Nerve Tissue Proteins; D009928:Organ Specificity; D010622:Phencyclidine / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D017480:Receptors, sigma / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D012756:Sheep; D013552:Swine
D001679:Biogenic Amines; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D011950:Receptors, Cholinergic; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D012701:Serotonin; D016291:Dizocilpine Maleate; D010622:Phencyclidine; D004298:Dopamine