Abstract
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.
Original language | English (US) |
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Pages (from-to) | 2-11 |
Number of pages | 10 |
Journal | Biological Psychiatry |
Volume | 43 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 1998 |
Keywords
- (-)- 3PPP
- Antipsychotic
- Autoreceptor
- Partial dopamine agonist
- Schizophrenia
ASJC Scopus subject areas
- Biological Psychiatry