Activators of sodium, calcium and potassium channels modulate the cardiac effects of quinidine in vitro.
Quinidine (25.5 mumol/l) reduced the beating frequency of isolated right guinea-pig atria, caused a negative inotropic effect in papillary muscles and slightly raised the contractile force of left atria. The functional refractory period of both tissues was prolonged. A 20% increase of the extracellular sodium concentration did not reverse the effects of quinidine. The Na-channel activator BDF 9148 (1 mumol/l) and the Ca-channel agonist Bay-K-8644 (0.5 mumol/l) further increased the contractile force and caused an additional prolongation of the functional refractory period in quinidine-pretreated atria. Only Bay-K-8644 was able to reverse the negative inotropic effect of quinidine in papillary muscles. The influence of Bay-K-8644 on the contractile force in quinidine-pretreated muscles was not attenuated by lemacalim (3 mumol/l), an activator of ATP-dependent potassium channels, but the duration of the functional refractory period was significantly reduced. These results suggest that a combination of a calcium channel activator and a potassium channel opener might be able to improve the treatment of quinidine intoxications.
Brasch
H
H
Institute of Pharmacology, Medical University of Lübeck, Germany.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001384:Azetidines / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D019806:Cromakalim; D004338:Drug Combinations; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects*
D001384:Azetidines; D001578:Benzopyrans; D002120:Calcium Channel Agonists; D002316:Cardiotonic Agents; D002317:Cardiovascular Agents; D004338:Drug Combinations; D015221:Potassium Channels; D011758:Pyrroles; D015222:Sodium Channels; D019806:Cromakalim; C071117:BDF 9148; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011802:Quinidine