title: Effects of S (+)-3-phenethyl-PP, a putative dopamine autoreceptors agonist with greater autoreceptor selectivity than 3-PPP enantiomers.
abstract: The experiments concerned the pharmacology of the enantiomers of the phenethyl-analogue (3-phenethyl-PP) of the putative dopamine (DA) autoreceptor agonist 3-PPP. In contrast to the almost equipotency of 3-PPP enantiomers, the phenethyl enantiomers showed marked stereoselectivity. S(+)-3-Phenethyl-PP had 25 times higher affinity to D-2 DA receptors in vitro than the R(-)-enantiomer. In vivo a similar potency difference was seen for the inhibition of motility, induction of circling behaviour in 6-OHDA-lesioned rats and emetic effect in dogs. None of the enantiomers induced stereotypy and hypermotility in normal rats or in rats pretreated with reserpine and alpha-methyl-p-tyrosine. In test models for antidopaminergic activity only slight activity of either enantiomer was observed. The S(+)-enantiomer had no antagonistic effect against apomorphine- and amphetamine-induced stereotypies, no cataleptogenic activity and only partially antagonized amphetamine-induced hypermotility. Apomorphine-induced emesis was weakly antagonized. The results indicate a greater and higher selectivity of S(+)-3-phenethyl-PP for DA receptors mediating sedation compared with 3-PPP enantiomers which previously have been shown to exert significant effects on postsynaptic DA receptors. Thus S(+)-3-phenethyl-PP may be a more selective model compound for the differential study of effects elicited by stimulation of pre- and postsynaptic DA receptors.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000932:Antiemetics; D002375:Catalepsy / Q000139:chemically induced; D004285:Dogs; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006633:Histamine Antagonists; D006801:Humans; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010276:Parasympatholytics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013237:Stereoisomerism; D013239:Stereotyped Behavior / Q000187:drug effects; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000932:Antiemetics; D006633:Histamine Antagonists; D010276:Parasympatholytics; D010880:Piperidines; D011954:Receptors, Dopamine; C042956:3-(3-hydroxyphenyl)-N-(2-phenethyl)piperidine; C026539:preclamol; D000262:Adenylyl Cyclases; D004298:Dopamine; D009638:Norepinephrine