Dopamine DA 1 receptor agonist activity of YM435 in the canine renal vasculature

Abstract

1. 1. The renal vasodilatory effect of YM435 was used as an index of its dopamine DA 1 receptor agonist activity and compared with that of dopamine in pentobarbital-anesthetized dogs. 2. 2. Intrarenal arterial administration of YM435 (0.1 to 10 μg) and dopamine (1 to 100 μg) produced a dose-dependent increase in renal blood flow. The doses of YM435 and dopamine required to cause a 30-ml/min increase in renal blood flow were 2.0 and 26.8 μg intra-arterially (IA), respectively. YM435 was therefore 13 times more potent than dopamine in this effect. 3. 3. The selective dopamine DA 1 receptor antagonist, SCH 23390, but not the selective dopamine DA 2 receptor antagonist, nemonapride, caused dose-dependent, parallel shifts to the right in the doseresponse curve of YM435. 4. 4. The present results demonstrate that YM435 is a potent and selective dopamine DA 1 receptor agonist.