Effects of 7-ethoxycarbonyl-4-hydroxymethyl-6,8-dimethyl-1(2H)-phthalazinone (EG 626), a new phosphodiesterase inhibitor, on the cardiovascular system of the dog.
7-Ethoxycarbonyl-4-hydroxymethyl-6,8-dimethyl-1(2H)-phthalazinone (EG 626) (0.3-3 mg/kg i.v.), a new cyclic AMP phosphodiesterase inhibitor, increased femoral, renal, coronary, carotid, vertebral and sagittal blood flows in anesthetized dogs. Systolic tension in left ventricular wall, heart rate and cardiac output also increased. These properties of EG 626 resembled those of papaverine (0.1-1 mg/kg i.v.). However, the heart rate increasing activity of EG 626 was less than that of papaverine at equipotent does on the vasodilator actions. In the isolated right atria of guinea pigs, EG 626 was more selective for increasing contractility than for increasing the sinus rate. The cardiovascular actions of EG 626 were also examined in perfused vascular beds and papillary muscle preparations of dogs. An i.v. infusion of EG 626 or papaverine (0.3 mg/kg/min) enhanced the increasing action of isoprenaline on left ventricular systolic pressure and coronary sinus outflow. The vasodilator effect of EG 626 was no suppressed by atropine, propranolol nor clemastine, and the inotropic action was not modified by pindolol. These results indicate that EG 626 may be a useful vasodilator with a cardiotonic activity but with less potency to cause tachycardia than papaverine.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010208:Papaverine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010793:Phthalazines / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects
D010726:Phosphodiesterase Inhibitors; D010793:Phthalazines; D011724:Pyridazines; C011329:phthalazinol; D010208:Papaverine; D007545:Isoproterenol