Cardiovascular and adenylate cyclase stimulating effects of colforsin daropate, a water-soluble forskolin derivative, compared with those of isoproterenol, dopamine and dobutamine.
Colforsin daropate is a recently developed water-soluble derivative of forskolin that directly stimulates adenylate cyclase, unlike the catecholamines. The chronotropic, inotropic and coronary vasodilator actions of colforsin daropate were compared with those of isoproterenol, dopamine and dobutamine, using canine isolated, blood-perfused heart preparations. The stimulating effect of each drug on adenylate cyclase activity was also assessed. Colforsin daropate, as well as each of the catecholamines, exerted positive chronotropic, inotropic and coronary vasodilator actions. The order of selectivity for the cardiovascular variables of colforsin daropate was coronary vasodilation >> positive inotropy > positive chronotropy; whereas that of isoproterenol, dopamine and dobutamine was positive inotropy >> coronary vasodilation > positive chronotropy. Thus, a marked characteristic of colforsin daropate is its potent coronary vasodilator action. On the other hand, each drug significantly increased the adenylate cyclase activity in a dose-related manner: colforsin daropate >> isoproterenol > dopamine = dobutamine. These results suggest that colforsin daropate may be preferable in the treatment of severe heart failure where the coronary blood flow is reduced and beta-adrenoceptor-dependent signal transduction pathway is down-regulated.
Yoneyama
Masahiko
M
Department of Pharmacology, Yamanashi Medical University, Tamaho-cho, Nakakoma-gun, Japan.
Sugiyama
Atsushi
A
Satoh
Yoshioki
Y
Takahara
Akira
A
Nakamura
Yuji
Y
Hashimoto
Keitaro
K
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects*; D005576:Colforsin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004280:Dobutamine / Q000494:pharmacology*; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D012995:Solubility; D014665:Vasodilator Agents / Q000494:pharmacology*; D014867:Water
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D015259:Dopamine Agents; D014665:Vasodilator Agents; D014867:Water; C122001:colforsin daropate; D005576:Colforsin; D004280:Dobutamine; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D004298:Dopamine