title: Synthesis and dopamine agonist and antagonist effects of (R)-(-)- and (S)-(+)-11-hydroxy-N-n-propylnoraporphine.
abstract: The R-(-) and S-(+) enantiomers of 11-hydroxy-N-n-propylnoraporphine, (R)-3 and (S)-3, were synthesized in six steps from 1-(3-methoxy-2-nitrobenzyl)isoquinoline. Neuropharmacological evaluation of the R and S isomers (by affinity to dopamine receptor sites in rat brain tissues, induction of stereotyped behavior, and interaction with motor arousal induced by (R)-apomorphine in the rat) indicated that, similar to the 10,11-dihydroxy congener 2, both enantiomers can bind to dopamine receptors but that only (R)-3 activates them, whereas (S)-3 shows activity as a dopaminergic antagonist.
authors.affiliation: Section of Medicinal Chemistry, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, Massachusetts 02115.
authors.forename: Y
authors.initials: Y
authors.lastname: Gao
authors.forename: R
authors.initials: R
authors.lastname: Zong
authors.forename: A
authors.initials: A
authors.lastname: Campbell
authors.forename: N S
authors.initials: NS
authors.lastname: Kula
authors.forename: R J
authors.initials: RJ
authors.lastname: Baldessarini
authors.forename: J L
authors.initials: JL
authors.lastname: Neumeyer
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001060:Aporphines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001143:Arousal / Q000187:drug effects; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D003342:Corpus Striatum / Q000378:metabolism; D018492:Dopamine Antagonists; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D013239:Stereotyped Behavior / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D001060:Aporphines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; C008081:11-hydroxy-N-(n-propyl)noraporphine; D001058:Apomorphine