Dopamine DA1 receptor agonist activity of YM435 in the canine renal vasculature.
1. The renal vasodilatory effect of YM435 was used as an index of its dopamine DA1 receptor agonist activity and compared with that of dopamine in pentobarbital-anesthetized dogs. 2. Intrarenal arterial administration of YM435 (0.1 to 10 micrograms) and dopamine (1 to 100 micrograms) 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 micrograms intra-arterially (IA), respectively. YM435 was therefore 13 times more potent than dopamine in this effect. 3. The selective dopamine DA1 receptor antagonist, SCH 23390, but not the selective dopamine DA2 receptor antagonist, nemonapride, caused dose-dependent, parallel shifts to the right in the dose-responsive curve of YM435. 4. The present results demonstrate that YM435 is a potent and selective dopamine DA1 receptor agonist.
Yatsu
T
T
Cardiovascular and Atherosclerosis Research Laboratories, Ibaraki, Japan. YATSU@YAMANOUCHI.CO.JP
Uchida
W
W
Inagaki
O
O
Tanaka
A
A
Takenaka
T
T
D000818:Animals; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D018818:Fenoldopam / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects; D044005:Tetrahydroisoquinolines; D014665:Vasodilator Agents / Q000494:pharmacology*
D018491:Dopamine Agonists; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D014665:Vasodilator Agents; D018818:Fenoldopam; C073504:zelandopam; D004298:Dopamine