Effects of a specific bradycardic agent (AQ-A39) and verapamil on beta-adrenergic responses in isolated guinea pig atria.
AQ-A39 (5,6-dimethoxy-2-[3-[(3,4-dimethoxy)phenylethyl)methylamino]propyl)- phthalimidine), a specific bradycardic agent, and verapamil, a calcium channel blocker, were studied for their ability to alter rate and force of contraction in the presence and absence of isoproterenol, a beta-adrenergic stimulant, using isolated guinea pig atria. Both compounds (10(-7)-10(-4) M) produced dose-related decreases in frequency of spontaneously beating right atria. Verapamil decreased, while AQ-A39 increased, the force of contraction of electrically stimulated (1.0 Hz) left atria. At equal negative chronotropic concentrations, AQ-A39 was more effective than verapamil in reducing the maximum isoproterenol-induced tachycardia. Verapamil, but not AQ-A39, antagonized positive inotropic responses to isoproterenol. Therefore, AQ-A39 differed from verapamil in that (i) AQ-A39 was a more selective bradycardic agent in both beta-adrenergically stimulated and nonstimulated preparations and (ii) AQ-A39 was more effective in reducing isoproterenol-elevated heart rate compared with basal heart rate. This profile of activities suggests that AQ-A39 will be beneficial in cardiac pathologies where sympathetic nervous system activity is elevated and a lowering of heart rate without a reduction in cardiac contractility is desired.
D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D054833:Isoindoles; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010797:Phthalimides / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D002317:Cardiovascular Agents; D054833:Isoindoles; D010797:Phthalimides; D011943:Receptors, Adrenergic, beta; D014700:Verapamil; D007545:Isoproterenol; C030532:falipamil