In vivo characterization of novel full and partial 2-(4-aminophenyl)-N,N-dipropylethylamine dopamine D-2 receptor agonists

Behavioral and biochemical techniques were used to compare the in vivo intr insic efficacy of two new 2-(4-aminophenyl)-N, N-dipropolylethylamine dopam ine D-2 receptor agonists, 2-(4-amino-3-trifluoromethylphenyl)-N-N-dipropyl -ethylamine (NBF-203) and 2-(4-amino-3-bromo-5-trifluoromethylphenyl)-N-N-d ipropylethylamine (NBF-234). Adult male Sprague-Dawley rats were used as ex perimental animals. NBF-203 was characterized as a full dopamine D-2 recept or agonist, whereas NBF-234 displayed properties of a partial agonist, or a ntagonist, at dopamine D-2 receptors. Thus, NBF-203 produced effects simila r to those of apomorphine in models for dopamine synthesis, release and tur nover. As a strong indication of markedly less intrinsic efficacy, the admi nistration of NBF-234 did not result in antagonism of reserpine-induced sup pression of locomotor activity in the presence of (+/-)-1-phenyl-2,3,4,5,-t etrahydro-(1H)-3-benzazepine-7,8-diol HCl (SKF-38393)-induced dopamine D-1 receptor activation. The present series of compounds offer the possibility of adjusting intrinsic efficacy at dopamine D-2 receptors, and such fine-tu ning could be an important strategy in the search for optimal antipsychotic or antiparkinson drugs within the partial dopamine D-2 receptor agonist co ncept. (C) 2000 Elsevier Science B.V. All rights reserved.