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.
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.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology; D000242:Cyclic AMP / Q000096:biosynthesis; D008297:Male; D008959:Models, Neurological; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D013237:Stereoisomerism
D010880:Piperidines; D011954:Receptors, Dopamine; C026539:preclamol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases