Aporphines. 39. Synthesis, dopamine receptor binding, and pharmacological activity of (R)-(-)- and (S)-(+)-2-hydroxyapomorphine.
The enantiomers (6aR and 6aS) of 2,10,11-trihydroxyaporphine (THA) were synthesized from thebaine and bulbocapnine and evaluated pharmacologically in vitro in comparison with (-)-apomorphine [(-)-APO] and dopamine by competition with tritiated apomorphine, ADTN, and spiroperidol for binding to a membrane fraction of calf caudate nucleus, as well as for ability to stimulate adenylate cyclase. In all four tests, the rank order of potency was (-)-APO greater than (-)-THA much greater than (+)-THA. Thus, these results extend the impression that the 6aR configuration for hydroxyaporphines is preferred for interactions with putative dopamine receptors and that 2-hydroxylation reduces potency in comparison with 10,11-dihydroxyaporphines.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D003342:Corpus Striatum / Q000201:enzymology; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D013237:Stereoisomerism
D011954:Receptors, Dopamine; C035558:2-hydroxyapomorphine; D000262:Adenylyl Cyclases; D001058:Apomorphine