Antipsychotic properties of the partial dopamine agonist (-)-3-(3- hydroxyphenyl)-N-n-propylpiperidine (preclamol) in schizophrenia

Adrienne C. Lahti, Martin A. Weiler, Patricia K. Corey, Robert A. Lahti, Arvid Carlsson, Carol A. Tamminga

Research output: Contribution to journalArticle

98 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)2-11
Number of pages10
JournalBiological Psychiatry
Volume43
Issue number1
DOIs
StatePublished - Jan 1 1998

Fingerprint

Dopamine Agonists
Antipsychotic Agents
Schizophrenia
Placebos
Cross-Over Studies
Brief Psychiatric Rating Scale
Tachyphylaxis
Therapeutic Uses
Pharmaceutical Preparations
Psychotic Disorders
preclamol
Therapeutics

Keywords

  • (-)- 3PPP
  • Antipsychotic
  • Autoreceptor
  • Partial dopamine agonist
  • Schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Antipsychotic properties of the partial dopamine agonist (-)-3-(3- hydroxyphenyl)-N-n-propylpiperidine (preclamol) in schizophrenia. / Lahti, Adrienne C.; Weiler, Martin A.; Corey, Patricia K.; Lahti, Robert A.; Carlsson, Arvid; Tamminga, Carol A.

In: Biological Psychiatry, Vol. 43, No. 1, 01.01.1998, p. 2-11.

Research output: Contribution to journalArticle

Lahti, Adrienne C. ; Weiler, Martin A. ; Corey, Patricia K. ; Lahti, Robert A. ; Carlsson, Arvid ; Tamminga, Carol A. / Antipsychotic properties of the partial dopamine agonist (-)-3-(3- hydroxyphenyl)-N-n-propylpiperidine (preclamol) in schizophrenia. In: Biological Psychiatry. 1998 ; Vol. 43, No. 1. pp. 2-11.
@article{b2e0730496844ca898a6b859bb624fcd,
title = "Antipsychotic properties of the partial dopamine agonist (-)-3-(3- hydroxyphenyl)-N-n-propylpiperidine (preclamol) in schizophrenia",
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.",
keywords = "(-)- 3PPP, Antipsychotic, Autoreceptor, Partial dopamine agonist, Schizophrenia",
author = "Lahti, {Adrienne C.} and Weiler, {Martin A.} and Corey, {Patricia K.} and Lahti, {Robert A.} and Arvid Carlsson and Tamminga, {Carol A.}",
year = "1998",
month = "1",
day = "1",
doi = "10.1016/S0006-3223(97)00030-9",
language = "English (US)",
volume = "43",
pages = "2--11",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "1",

}

TY - JOUR

T1 - Antipsychotic properties of the partial dopamine agonist (-)-3-(3- hydroxyphenyl)-N-n-propylpiperidine (preclamol) in schizophrenia

AU - Lahti, Adrienne C.

AU - Weiler, Martin A.

AU - Corey, Patricia K.

AU - Lahti, Robert A.

AU - Carlsson, Arvid

AU - Tamminga, Carol A.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - 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.

AB - 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.

KW - (-)- 3PPP

KW - Antipsychotic

KW - Autoreceptor

KW - Partial dopamine agonist

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=0031963973&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031963973&partnerID=8YFLogxK

U2 - 10.1016/S0006-3223(97)00030-9

DO - 10.1016/S0006-3223(97)00030-9

M3 - Article

C2 - 9442338

AN - SCOPUS:0031963973

VL - 43

SP - 2

EP - 11

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 1

ER -