Interaction of two phencyclidine opiate-like derivatives with 3H-opioid binding sites.

Small modifications of the basic structure of phencyclidine have produced compounds with potent opioid analgesic actions. Detailed competition studies show that two of these phencyclidine derivatives, the 3'-hydroxy and the 4-phenyl-4-hydroxy analogs, displace 3H-opioid binding in a multiphasic manner. Approximately 25% of the total specific binding of all the radiolabeled opioids is displaced by low concentrations of the derivatives while the remainder of the binding is far less sensitive. The inclusion of these derivatives in saturation studies with [3H]dihydromorphine indicate that both compounds interact with highest affinity with mu1 sites. Furthermore, the prior in vivo administration of naloxonazine 24 h earlier reduces the analgesic potency of the 4-phenyl-4-hydroxy compound by 63% supporting a mu1 mechanism of action.