Synthesis and dopamine agonist and antagonist effects of (R)-(-)- and (S)-(+)-11-hydroxy-N-n-propylnoraporphine.
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.
Gao
Y
Y
Section of Medicinal Chemistry, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, Massachusetts 02115.
Zong
R
R
Campbell
A
A
Kula
N S
NS
Baldessarini
R J
RJ
Neumeyer
J L
JL
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
D001060:Aporphines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; C008081:11-hydroxy-N-(n-propyl)noraporphine; D001058:Apomorphine