Metaphit, a proposed phencyclidine receptor acylator: phencyclidine-like behavioral effects and evidence of absence of antagonist activity in pigeons and in rhesus monkeys.

Abstract

Metaphit, a derivative of phencyclidine (PCP), binds irreversibly to PCP sites and appears to act as an antagonist of PCP under some conditions and as a PCP-like agonist under other conditions. To describe further these conditions, the authors investigated the behavioral effects of metaphit by using different routes of administration, behavioral procedures and species. In pigeons, metaphit induced PCP-like catalepsy after i.c.v. administration and, after i.m. administration, produced PCP-like discriminative stimulus effects and stereotyped operant responding. In rhesus monkeys, metaphit produced ataxia and convulsions but did not induce catalepsy, anesthesia or PCP-like discriminative stimulus effects. None of the effects of PCP-type drugs [i.e., PCP, ketamine or (+/-)-SKF 10,047] in pigeons or rhesus monkeys was antagonized by metaphit. Metaphit potentiated the discriminative stimulus effects of PCP and of SKF 10,047 in pigeons. These results suggest that metaphit acts not as an antagonist of PCP but as a PCP-like agonist under these conditions. Metaphit's potentiation of behavioral effects of PCP may be related to the presumed ability of metaphit to acylate PCP receptors. The extent to which metaphit produces PCP-like behavioral effects in part may be species dependent.