Cardiovascular effects of methylflavonolamine hydrochloride (SIPI-549) in cross-circulated canine atrial and ventricular preparations.
The cardiovascular effects of SIPI-549 [4'-methyl-7-(2-hydroxy-3-isopropylaminoproxy)-flavone hydrochloride] were investigated in isolated canine atrial and ventricular muscles perfused with heparinized arterial blood from a donor dog. When SIPI-549 was administered intravenously to the intact donor dog, a slight hypotension was induced in a dose range of 0.01 to 3 mumol/kg. At the same time, slight negative chronotropic and inotropic responses appeared in isolated and perfused atria, suggesting a cardiac depressant action. Direct administration of SIPI-549 into the cannulated sinus node artery of the isolated atrium produced negative inotropic and biphasic chronotropic responses in a dose related manner (0.01-1 mumol). SIPI-549 also induced a dose-dependent decrease in developed tension of the isolated left ventricle. The SIPI-549-induced negative chronotropic and inotropic effects were not modified by atropine in doses which blocked carbachol-induced negative chronotropic and inotropic effects. The SIPI-549-induced positive chronotropic effects were inhibited by propranolol but significantly potentiated by imipramine treatment, indicating that a large dose of SIPI-549 produces a release of catecholamine via a non-tyramine like action. Large doses of SIPI-549 did not significantly affect norepinephrine-induced positive chronotropic effects. These results indicate that SIPI-549 may have non-cholinergic cardiac depressant properties and no beta-adrenoceptor blocking activity. However, it appears to elicit a release of catecholamines in a non-tyramine-like manner at relatively large doses.
Chiba
S
S
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Akabane
K
K
Furukawa
Y
Y
Karasawa
Y
Y
D000319:Adrenergic beta-Antagonists; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003427:Cross Circulation / Q000379:methods; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D005419:Flavonoids; D044948:Flavonols; C052073:SIPI 549