In Vitro Effect of the Racemic Mixture and the (-)enantiomer of N-n-propyl-3-(3-hydroxyphenyl)-piperidine (3-PPP) on Postsynaptic Dopamine Receptors and on a Presynaptic Dopamine Autoreceptor

Overview

Journal J Neural Transm

Specialties Neurology
Physiology

Date 1983 Jan 1

PMID 6317801

Citations 6

Authors

R Markstein

D Lahaye

Affiliations

Soon will be listed here.

Abstract

The racemic mixture and the (-)enantiomer of the putative dopamine autoreceptor agonist 3-PPP were investigated in vitro using dopamine-sensitive adenylate cyclase in homogenates of rat striatum as a model for a postsynaptic D1-receptor type and inhibition of electrically-evoked tritium overflow from rat striatal slices preincubated with [3H]choline and [3H]dopamine as a model for a postsynaptic D2- and a presynaptic dopamine autoreceptor type, respectively. In contrast, to apomorphine, neither the racemic mixture nor the (-)enantiomer exerted any effect, suggesting agonistic properties in all three receptor models. However, both (+/-)3-PPP and (-)3-PPP were weak antagonists at postsynaptic D1- and D2-receptors. The results of the present investigation suggest that the in vivo effects of 3-PPP are either the result of metabolic activation or that this drug activates an other dopamine autoreceptor type, pharmacologically different from that one modulating dopamine release.

Citing Articles

Psychotomimetic opiate receptors labeled and visualized with (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine.

Largent B, Gundlach A, Snyder S Proc Natl Acad Sci U S A. 1984; 81(15):4983-7.

PMID: 6087359 PMC: 391617. DOI: 10.1073/pnas.81.15.4983.

An electrophysiological analysis of the actions of the 3-PPP enantiomers on the nigrostriatal dopamine system.

Clark D, Engberg G, Pileblad E, Svensson T, Carlsson A, Freeman A Naunyn Schmiedebergs Arch Pharmacol. 1985; 329(4):344-54.

PMID: 4033804 DOI: 10.1007/BF00496366.

Dopamine-receptor agonists: mechanisms underlying autoreceptor selectivity. I. Review of the evidence.

Clark D, Hjorth S, Carlsson A J Neural Transm. 1985; 62(1-2):1-52.

PMID: 3894582 DOI: 10.1007/BF01260414.

Comparison between radiolabelled and endogenous dopamine release from rat striatal slices: effects of electrical field stimulation and regulation by D2-autoreceptors.

Herdon H, Nahorski S Naunyn Schmiedebergs Arch Pharmacol. 1987; 335(3):238-42.

PMID: 3587370 DOI: 10.1007/BF00172790.

Dopamine D2 receptors in brain and anterior pituitary recognize agonist and antagonist actions of (-)-3-PPP.

George S, Watanabe M, Seeman P J Neural Transm. 1985; 64(1):13-33.

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