Abstract
The effects of gallopamil, D600, a methoxy derivative of verapamil, on the mechanical and electrophysiological parameters of isolated guinea-pig myocardial preparations were compared with those of verapamil. Both gallopamil and verapamil produced concentration-dependent negative chronotropic and negative inotropic effects in isolated right atrial and right ventricular papillary muscles, respectively. The negative chronotropic and negative inotropic potencies of gallopamil were 7.2 and 4.3 times higher than those of verapamil, respectively. Gallopamil decreased the action potential duration of isolated papillary muscles without substantially affecting other action potential parameters, while verapamil decreased not only the action potential duration but also the maximum rate of rise and amplitude. In voltage-clamped single ventricular myocytes, gallopamil as well as verapamil decreased the L-type Ca2+ current amplitude. The potency orders for the shortening of the action potential duration and inhibitory effects of the L-type Ca2+ current amplitudes were verapamil > gallopamil. These results indicate that gallopamil has higher negative chronotropic and inotropic potency than verapamil as a result of factors other than L-type Ca2+ current inhibition.
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