Phencyclidine (PCP) and sigma receptors, though linked in terms of their historical development, and their generally high affinity interactions with (+)-opiates, are now known to be pharmacologically and biochemically distinct binding sites. The PCP binding site, because it is but one component of the NMDA receptor, is relevant to drug abuse research because the NMDA receptor plays important roles in neuronal processes involved in substance abuse, such as memory, propagation of seizures and kindling, tolerance and dependence. Previous studies showed that the PCP analog, [3H]TCP labels two high affinity PCP binding sites: PCP site 1 (NMDA-receptor-associated) and PCP site 2 (biogenic-amine -transporter- associated). Collaborative investigations with Dr. F. Ivy Carroll lead to the discovery of RTI-4793-14, which has high potency and selectivity for PCP site 2. This fiscal year, a more potent analog, RTI-4793-41, was discovered which exhibits the type of in vitro activity predictive of antideporessant properties in humans. A patent application on these compounds was issued. Behavioral studies also suggest that certain PCP site 2 ligands show promise as potential anti-craving medications. As such, the strong association of high risk behaviors related to the spread of HIV with cocaine addiction makes the effort to develop new treatment medications for addiction highly related to the fight against AIDS.
