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Cardioselective effects of gallopamil compared with verapamil in the dog heart
K Takahashi1, K Tsuchida, H Aihara
1Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Abstract:
The cardiac and coronary vasodilator effects of gallopamil and verapamil were compared in isolated, blood-perfused papillary muscle, sinoatrial (SA) node and atrioventricular (AV) node preparations of the dog. Gallopamil and verapamil (0.3-100 micrograms) were injected intra-arterially. In all preparations, gallopamil produced an equipotent but longer-lasting increase in coronary blood flow compared to verapamil. In paced papillary muscle preparations, both drugs reduced the force of contraction. In spontaneously beating papillary muscle preparations, both drugs had virtually no effect on the ventricular rate. In SA node preparations, both drugs reduced the sinus rate and produced atrial standstill at medium and large doses. In AV node preparations, both drugs prolonged the AV conduction time and produced second- or third-degree AV block at medium and large doses only when injected into the artery supplying the AV node, but not when injected into the artery supplying the His-Purkinje-ventricular system. The cardiac effects of gallopamil described above were 2-3 times more potent and were longer-lasting than those of verapamil. These results suggest that gallopamil is more selective for myocardium (papillary muscle, SA node or AV node) than for coronary vasculature compared with verapamil in isolated, blood-perfused heart preparations of the dog.