Background: In an ongoing effort to characterize the clinical pharmacologic profile of the partial dopamine agonist (-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine [(-)-3PPP], we administered it to drug-free schizophrenic patients in two consecutive studies.
Methods: In a preliminary dose-finding study, 9 patients were treated using a 6-week placebo-controlled crossover design. Then, to properly demonstrate the antipsychotic effect, we carried out an early efficacy study; here 10 patients received (-)-3PPP, 300 mg B.I.D., in a 1-week placebo-controlled crossover study.
Results: Dose-Finding Study: (-)-3PPP showed apparent antipsychotic effect in repeated dosing, with 300 mg B.I.D. being the most effective dose for antipsychotic action; however, the apparent antipsychotic action was not sustained for longer than 1 week, presumably because of desensitization of the receptor by the agonist. Early Efficacy Study: Positive symptoms as measured by the Psychosis Change Scale decreased in 1 week by 30% with (-)-3PPP compared to placebo, and negative symptoms measured with the Brief Psychiatric Rating Scale Withdrawal subscale decreased by 28% with the drug. In both studies, (-)-3PPP lacked any evidence of motor side effects.
Conclusions: These data show that psychotic symptoms decrease with (-)-3PPP and suggest that the treatment of schizophrenia with partial dopamine agonist is a promising strategy. Future attention will be directed toward testing techniques to diminish the tachyphylaxis to allow an ongoing therapeutic effect.