title: Cardiotonic effect of phthalazinol (EG-626) in the isolated guinea pig by myocardium: mechanical and electrophysiological study.
abstract: EG-626, 7-ethoxycarbonyl-6, 8-dimethyl-4-hydroxymethyl-1 (2H)-phthalazinone, was found to be a considerably potent cardiotonic agent. It produced both the positive chronotropic and inotropic actions in the guinea pig heart muscle. Positive inotropic action of isoproterenol was potentiated by EG-626 at the concentration which did not produce a substantial positive inotropic action by itself. Cardiac action potential was not modified by EG-626 at concentrations sufficient to produce positive inotropic actions. EG-626 has a strong activity to produce slow responses in the depolarized myocardium, indicating that it can increase the density of the slow channels. The possibility was shown that the increase in the density of the slow channel may play an important role in the positive inotropic action of EG-626. The increase in the intracellular cyclic AMP due to the phosphodiesterase inhibition is tentatively most likely to be the cause of the EG-626 induced in the density of the slow channels.
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010208:Papaverine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D010793:Phthalazines / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D013806:Theophylline / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D010793:Phthalazines; D011724:Pyridazines; C011329:phthalazinol; D013806:Theophylline; D010208:Papaverine; D011188:Potassium