Influence of the alpha-adrenoceptor antagonist urapidil on transmembrane action potentials of mammalian myocardium.
6-[3-[4-(o-Methoxyphenyl)-1-piperazinyl]-propylamino)-1, 3-dimethyluracil (urapidil, Ebrantil) is capable of significantly influencing the excitation processes of the mammalian myocardial cell in a dose-related manner. At a concentration of 10(-3) mol/l urapidil myocardial action potentials of guinea-pig and hypertrophied or nonhypertrophied rat hearts reveal substantial reduction of the maximum upstroke velocity and marked prolongation. All these effects can completely be washed out within 15 min. Decreased isometric peak tension and time to peak tension indicate that high urapidil concentrations exert an additional negative inotropic effect. Experimental blockade of the individual transmembrane ionic fluxes suggests that urapidil affects the cardiac excitation process in an antiarrhythmic-like manner with inhibition of the initial, rapid Na+ inward current; the repolarizing K+ efflux; and probably also the slow Ca++ inward current. 10(-6) mol/l urapidil does not induce any alteration in the electrical behaviour of myocardium. Since this concentration corresponds to the serum concentrations generally reached in oral therapy of hypertension with urapidil, antiarrhythmic side effects should only occur under exceptional conditions like parenteral administration of high dosage or increased myocardial sensitivity.
D000200:Action Potentials / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D010879:Piperazines / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D007473:Ion Channels; D010879:Piperazines; D012964:Sodium; C015568:urapidil; D011188:Potassium; D002118:Calcium