Action of dimethindene on the electrophysiological and mechanical properties of atrial and ventricular myocardium of guinea-pig.
The effect of dimethindene (DMI) on transmembrane potentials and contractile force was studied in atrial and ventricular myocardium of guinea-pigs. DMI reduced the maximum rate of depolarization (Vmax) without changing the resting potential in both preparations. In ventricular myocardium, DMI shortened the action potential duration and exerted a negative inotropic effect. In atrial muscle, the drug prolonged the action potential duration and induced a positive inotropic effect which could be antagonized with neither the alpha-blocker phentolamine, nor the beta-blocker pindolol, H1-blocker mepyramine and H2-blocker cimetidine. DMI had no effect on the slow action potentials induced by caffeine in K+-depolarized myocardial preparations. The drug consistently shifted the sodium inactivation curve to more negative membrane potentials. The results suggest that DMI has a quinidine-like membrane-stabilizing property, which may be due to its fast Na+ channel blocking activity. The differential inotropic action of the drug in atrial and ventricular myocardium is discussed.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D004115:Dimethindene / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004594:Electrophysiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009132:Muscles / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D010646:Phentolamine / Q000494:pharmacology; D010869:Pindolol / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D013268:Stimulation, Chemical
D004115:Dimethindene; D002927:Cimetidine; D010869:Pindolol; D011738:Pyrilamine; D010646:Phentolamine