Document Report Card

ID: ALA1122119

Journal: J Med Chem

Title: Aporphines. 39. Synthesis, dopamine receptor binding, and pharmacological activity of (R)-(-)- and (S)-(+)-2-hydroxyapomorphine.

Authors: Neumeyer JL, Arana GW, Ram VJ, Kula NS, Baldessarini RJ.

Abstract: 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.

CiteXplore: 7120288

DOI: 10.1021/jm00350a021