Antagonism of Phencyclidine (PCP)-Induced Behavior and Binding in Rats by a Specific PCP Receptor Alkylating Agent Administered I.V.
Phencyclidine (PCP), originally a general anesthetic but no longer used on humans because of schizophrenic-like side-effects, is a major drug of abuse in the U.S. PCP specifically binds to its receptors, inducing its behavioral effects through various neurotransmitter systems. Recently, a PCP receptor alkylating agent, Metaphit, has been shown to antagonize receptor binding and PCP-induced behavior when administered intracerebroventricularly. This study dealt with Metaphit's antagonistic ability when administered intravenously. In vivo behavioral studies and binding analysis were carried out. Metaphit definitely crossed the blood-brain barrier and alkylated PCP receptors. Metaphit was also found to antagonize PCP-induced stereotypy but not ataxia. This raises several questions as to how PCP actually induces ataxia. Although further investigation must be done, Metaphit may have definite therapeutic potential in the treatment of PCP intoxication and psychotic disorders.