Aporphine enantiomers. Interactions with D-1 and D-2 dopamine receptors.
The R(-) and the S(+) enantiomers of apomorphine (APO) and N-n-propyl norapomorphine (NPA) interact with both the D-1 and the D-2 dopamine receptors. R(-)-APO, as well as R(-)- and S(+)-NPA, stimulates the D-1 dopamine receptor in carp retina; S(+)-APO blocks this dopamine receptor. Similarly, R(-)-APO, as well as R(-)- and S(+)-NPA, stimulates the D-2 dopamine receptor in the intermediate lobe of the rat pituitary gland; S(+)-APO blocks the intermediate lobe D-2 receptor. The interactions between these aporphine enantiomers and the D-1 and the D-2 dopamine receptors exemplify several manifestations of the previously described "n-propyl phenomenon." Because S(+)-APO is distinguished from the other tested aporphines by its ability to antagonize either the D-1 or the D-2 dopamine receptors, it is hypothesized that the presence of an N-methylated tertiary amine in a molecule of appropriate configuration can confer dopamine receptor antagonist activity to the molecule.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D002347:Carps; D007536:Isomerism; D007700:Kinetics; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012160:Retina / Q000378:metabolism; D013329:Structure-Activity Relationship
D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001058:Apomorphine