精神異常発現薬Phencyclidineの最近の話題

抄録

Phencyclidine (PCP) is a major drug of abuse in the United States. It is a particularly interesting pharmacological tool because it induces psychosis (known as PCP-induced psychosis) in man, which has been diagnosed initially as schizophrenia, and also induces amnesia. In the present review, recent results of experiments with PCP are discussed. The presence of an endogenous ligand for PCP receptors has been strongly suggested since the presence of highly specific and selective binding sites for PCP in the brain has been discovered. The endogenous factors that inhibit the binding of [³H] PCP and produce PCP-like pharmacological activity have been isolated from porcine, bovine and guinea-pig brains. PCP and sigma opioids may act through the same binding sites, since the psychotomimetic benzomorphans, classed as sigma opioids, inhibit binding of [³H] PCP and show PCP-like actions in several behavioral assays. However, recent works by a number of investigators indicate that PCP binding sites and sigma opioid sites may be distinct due to differences in drug selectivity and regional distribution. Metaphit, a derivative of PCP has been synthesized and identified as a rapid and specific site-directed acylating agent of PCP receptors in rat brain. The antagonistic effect of PCP on excitation of central mammalian neurons by N-methyl-D-aspartate (NMDA) and the function of NMDA receptors associated with learning and memory mechanisms have been reviewed. We have attempted to develop an animal model for the negative symptoms of schizophrenia since there is no animal model although many patients have exhibited negative symptoms. We have proposed that PCP-induced head-twitch, head-weaving and immobilization can be used as the model of negative symptoms.