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

Behavioral and biochemical techniques were used to compare the in vivo intrinsic efficacy of two new 2-(4-aminophenyl)-N, N-dipropylethylamine dopamine 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-dipropylethylamine (NBF-234). Adult male Sprague-Dawley rats were used as experimental animals. NBF-203 was characterized as a full dopamine D(2) receptor agonist, whereas NBF-234 displayed properties of a partial agonist, or antagonist, at dopamine D(2) receptors. Thus, NBF-203 produced effects similar to those of apomorphine in models for dopamine synthesis, release and turnover. As a strong indication of markedly less intrinsic efficacy, the administration of NBF-234 did not result in antagonism of reserpine-induced suppression of locomotor activity in the presence of (+/-)-1-phenyl-2,3,4,5, -tetrahydro-(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-tuning could be an important strategy in the search for optimal antipsychotic or antiparkinson drugs within the partial dopamine D(2) receptor agonist concept.