Semi-rigid analogs of dopamine such as 2-amino-6, 7-dihydroxytetrahydronaphthalene (A-6,7-DTN) and 2-amino-5,6-dihydroxytetrahydronaphthalene (A-5,6-DTN) as well as dialkylated derivatives of A-5,6-DTN were tested for dopamine-agonist activity on intact rabbit retina by measuring cyclic AMP formation. Thioxanthene neuroleptics of cis- (Z) or trans- (E) conformation were tested for dopamine antagonist activity on the same preparation by measuring the inhibition of dopamine-elicited accumulation of cyclic AMP. It is shown that A-6,7-DTN, which displays the trans β rotamer conformation of dopamine, is more potent than A-5,6-DTN, which displays the trans α rotamer conformation. However, dialkylation of A-5,6-DTN on the nitrogen can increase the dopamine-mimetic activity of this type of analog. Only cis- (or Z) thioxanthenes, which are clinical neuroleptics were able to inhibit the cyclic AMP formation induced by dopamine, in contrast to the lack of antagonist activity of trans- (or E) thioxanthenes. The latter isomers are also totally devoid of therapeutic benefit in man. It is concluded that stereochemical specificity exists for agonist- as well as for antagonist-agents supposed to interact with CNS dopamine receptors at a post-synaptic level and that such structural investigations can be selectively performed with rabbit retina in vitro.
|Original language||English (US)|
|Number of pages||5|
|Journal||Journal de Physiologie|
|State||Published - 1978|
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