Effects of neuroleptics on phencyclidine (PCP)-induced locomotor stimulation in mice

A variety of neuroleptics were compared for their ability to block phencyclidine (PCP)-induced behavioral stimulation in mice. Methiothepin, fluphenazine, trifluoperazine, and chlorpromazine were highly effective in blocking phencyclidine-induced stimulation at doses that did not decrease spontaneous behavioral activity. Clozapine, thioridazine and haloperidol were moderately effective, while sulpiride, molindone, and pimozide were completely ineffective. The effectiveness of the drugs was found to be correlated with their ability to block tryptamine-induced seizures and with several other measures of antidopaminergic and antiserotonergic potency. it is concluded that a combination of antidopaminergic and antiserotonergic activity is important for blocking the stimulating effects of phencyclidine.