title: Synthesis and neuropharmacological evaluation of esters of R(-)-N-alkyl-11-hydroxy-2-methoxynoraporphines.
abstract: We synthesized several esters of R(-)-N-alkyl-11-hydroxy-2-methoxynoraporphines, assessed their affinities at dopamine D(1) and D(2) receptors in rat forebrain tissue and quantified their effects on motor activity in normal adult male rats. Tested compounds displayed moderate to high affinities to D(2) receptors but low affinities to D(1) receptors. The most D(2)-potent (K(i)=18.9nM) and selective novel agent (>529-fold vs D(1) sites) was R(-)-2-methoxy-11-acetyloxy-N-n-propylnoraporphine (compound 4b). At moderate doses, the compound proved to have prolonged behavioral locomotor activity.
authors.affiliation: Alcohol Drug Abuse Research Center and Mailman Research Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
authors.forename: Yu-Gui
authors.initials: YG
authors.lastname: Si
authors.forename: Yong-Kee
authors.initials: YK
authors.lastname: Choi
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* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000138:chemical synthesis; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016548:Prosencephalon; D011485:Protein Binding; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D001060:Aporphines; D004952:Esters; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2