title: Synthesis and binding studies of 2-O- and 11-O-substituted N-alkylnoraporphines.
abstract: We synthesized several novel 2-O- or 11-O-substituted N-alkylnoraporphines and assessed their affinities at dopamine D(1) and D(2), and serotonin 5-HT(1A) receptors in rat forebrain tissue. Tested compounds displayed moderate to high affinities to D(2) receptors but low affinities to D(1) and 5HT(1A) receptors. The findings accord with previous evidence of a lipophilic cavity on the surface of the D(2) receptor to accommodate N-alkyl moieties of aporphines. The most D(2)-potent (K(i)=97 nM) and selective novel agent (>100-fold vs. D(1) and 5-HT(1A) sites) was R(-)-2-(2-hydroxyethoxy)-11-hydroxy-N-n-propylnoraporphine (compound 11).
authors.affiliation: Alcohol Drug Abuse Research Center and Mailman Research Center, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
authors.forename: Yu-Gui
authors.initials: YG
authors.lastname: Si
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Gardner
authors.forename: Frank I
authors.initials: FI
authors.lastname: Tarazi
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Baldessarini
authors.forename: John L
authors.initials: JL
authors.lastname: Neumeyer
mesh_terms: D000818:Animals; D001060:Aporphines / Q000138:chemical synthesis* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D007700:Kinetics; D008956:Models, Chemical; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry; D017447:Receptors, Dopamine D1 / Q000737:chemistry; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000378:metabolism
chemical_list: D001060:Aporphines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D044282:Receptor, Serotonin, 5-HT1A; C081279:aporphine; C008081:11-hydroxy-N-(n-propyl)noraporphine