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

Abstract

The racemic mixture and the (−)enantiomer of the putative dopamine autoreceptor agonist 3-PPP were investigatedin vitro using dopaminesensitive 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 thein 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 doopamine release.