Electromechanical effects of caroverine, a new slow-channel blockade, on the SA node cells of rabbit and atrial muscle fibers of rabbit and guinea pig.
The effects of caroverine on electrical activity of isolated rabbit sinoatrial (SA) node cells and atrial muscle fibers and on contractile force of atrial muscle preparations were examined. In spontaneously firing SA node cells, caroverine (1 X 10(-7) M-1 X 10(-5) M) decreased the action potential amplitude (APA) and the maximal rate of depolarization (MRD) in a concentration-dependent manner. However, the spontaneous firing cycle length of these cells was not prolonged significantly with the drug except at a high concentration. In constantly driven atrial muscle fibers, caroverine at the same concentration range shortened the 30% repolarization time coupled with a depression of the plateau phase of action potentials. The effects of caroverine on the developed tension (DT) of atrial muscle were compared with that of verapamil. The 50% effective dose (ED50) for inhibition on atrial DT was 1 X 10(-5) M for caroverine and 8 X 10(-8) M for verapamil. Caroverine as well as verapamil had a frequency-dependent inhibitory action on atrial DT, which indicates that both of the drugs have an influence on the kinetics of slow channel of cardiac fibers. In conclusion, it is suggested that caroverine has only a small negative inotropic effect while electrophysiological effects are similar to slow-channel blockers.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology*; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D012849:Sinoatrial Node / Q000187:drug effects*
D002121:Calcium Channel Blockers; D007473:Ion Channels; D011810:Quinoxalines; C000957:caroverine