Effects of cyproheptadine on electrophysiological properties of isolated cardiac muscle of dogs and rabbits

The effects of cyproheptadine were studied on cardiac Purkinje and ventricular muscle fibres of the dog and on cells of the sinoatrial (SA) node region of rabbit hearts, by means of electrophysiological techniques. Cyproheptadine (2-8 microM) decreased, in a dose-dependent manner, the plateau amplitude and the action potential duration to 50% repolarization of Purkinje and ventricular muscle cells. Higher concentrations also depressed the action potential amplitude, the overshoot and the maximum rate of rise of the upstroke. These effects were only partially reversed on washing. A four fold increase in Ca concentration of the standard Tyrode solution antagonized the effects of cyproheptadine on the action potential characteristics. The 'slow response' obtained in K-depolarized isoprenaline-treated fibres was blocked by cyproheptadine (4 microM). Cyproheptadine (10 microM) depolarized and suppressed the automaticity of spontaneously beating Purkinje fibres. The frequency of discharge of the SA node cells was slowed or abolished by cyproheptadine (2-4 microM). Atropine (2.6 microM) did not affect the negative chronotropic effect, whereas adrenaline (5 microM) reversed it. It is suggested that cyproheptadine depresses the slow inward current in all types of myocardial fibres studied. Higher concentrations might also affect the fast inward sodium current system.