Calcium channel antagonistic effects of AH-1058, a novel antiarrhythmic drug, on guinea-pig myocardium.
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.
Tanaka
H
H
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi, Chiba, Japan.
Ichikawa
T
T
Matsui
S
S
Okazaki
K
K
Masumiya
H
H
Kawanishi
T
T
Shigenobu
K
K
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004357:Drug Synergism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D001643:Bridged Bicyclo Compounds; D002121:Calcium Channel Blockers; D010880:Piperidines; D007545:Isoproterenol; C119283:AH 1058