In vivo dopamine autoreceptor selectivity appears to be critically dependent upon the aromatic hydroxyl position in a series of N,N-disubstituted 2-aminotetralins.
The potencies of a number of 2-aminotetralin derivatives as centrally acting dopamine (DA) receptor agonists were investigated using the reversal of the gamma-butyrolactone-induced increase in rat central DA biosynthesis rate as a measure of potency at DA autoreceptors and the reversal of the reserpine-induced immobility of mice as a measure of postsynaptic DA receptor stimulating potency. The results indicated that the compounds fell into two separate groups depending on their effectiveness in the postsynaptic test model. High postsynaptic effectiveness was achieved with compounds bearing a hydroxyl group at the 5 position of the aminotetralin structure, whereas aminotetralins lacking this substitution pattern were found to possess high DA autoreceptor selectivity. The observed dichotomy of DA agonists is discussed in relation to the possible involvement of multiple DA receptors and alpha-adrenoceptors.
D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D010891:Piribedil / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D012110:Reserpine / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D009281:Naphthalenes; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; C006561:2-aminotetralin; D004295:Dihydroxyphenylalanine; D012110:Reserpine; D010891:Piribedil; D001058:Apomorphine; D015107:4-Butyrolactone