Tanaka H, Ichikawa T, Matsui S, Okazaki K, Masumiya H, Kawanishi T, Shigenobu K
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi, Chiba, Japan.
Res Commun Mol Pathol Pharmacol. 1999;104(1):13-21.
Effects of AH-1058, a novel cyproheptadine derivative with high antiarrhythmic activity in in vivo arrhythmia models, were studied in guinea-pig myocardium. In coronary-perfused right ventricular tissue preparations, AH-1058 (10(-5) M) shortened the action potential duration with little effect on the resting membrane potential, maximum rate of rise and overshoot. AH-1058, 10(-7) M to 10(-5) M, concentration-dependently decreased the contractile force. The increase in contractile force by Ca2+ was markedly inhibited by 3 x 10(-6) M AH-1058 while that by isoproterenol was only slightly affected. In isolated ventricular myocytes, AH-1058 concentration-dependently decreased the nicardipine sensitive transient inward current with no effect on steady state currents, and decreased the amplitude of the evoked Ca2+ transient. These results suggest that AH-1058 has Ca2+ channel antagonistic effects which may contribute to its antiarrhythmic activity.
在豚鼠心肌中研究了新型具有高抗心律失常活性的赛庚啶衍生物AH - 1058在体内心律失常模型中的作用。在冠状动脉灌注的右心室组织制备物中，AH - 1058（10^(-5)M）缩短了动作电位持续时间，对静息膜电位、最大上升速率和超射影响很小。10^(-7)M至10^(-5)M的AH - 1058浓度依赖性地降低了收缩力。3×10^(-6)M的AH - 1058显著抑制了Ca2+引起的收缩力增加，而异丙肾上腺素引起的收缩力增加仅受到轻微影响。在分离的心室肌细胞中，AH - 1058浓度依赖性地降低了尼卡地平敏感的瞬时内向电流，对稳态电流无影响，并降低了诱发的Ca2+瞬变的幅度。这些结果表明，AH - 1058具有Ca2+通道拮抗作用，这可能有助于其抗心律失常活性。
