Antipsychotic properties of the partial dopamine agonist (-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine(preclamol) in schizophrenia.
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.
Lahti
A C
AC
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore 21228, USA.
Weiler
M A
MA
Corey
P K
PK
Lahti
R A
RA
Carlsson
A
A
Tamminga
C A
CA
D000328:Adult; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology
D000978:Antiparkinson Agents; D014150:Antipsychotic Agents; D010880:Piperidines; C026539:preclamol