The antiarrhythmic profile and cardiohemodynamic effect of a novel Ca(2+) channel blocker, 4-(5H-Dibenzo[a, d]cyclohepten-5-ylidene)-1-[(E)-3-(3-methoxy-2-nitro)phenyl-2-p ropeny l]
piperidine hydrochloride (AH-1058), were analyzed using the
epinephrine-, digitalis- and two-stage coronary
ligation-induced canine ventricular
arrhythmia models.
Intravenous administration of
AH-1058 (100 microg/kg) effectively suppressed each of the ventricular arrhythmias accompanied by weak hypotensive effects. The results contrast well with those of a typical Ca(2+) channel blocker,
verapamil, which suppresses only the
epinephrine-induced ventricular
arrhythmia with severe
hypotension. These results indicate that
AH-1058 may possess a more selective inhibitory action on Ca(2+) channels in the heart than on those in the vessels. Furthermore, the antiarrhythmic actions of
AH-1058 were slower in onset and longer-lasting, than those in our previous studies using other
antiarrhythmic drugs, including Na(+) and Ca(2+) channel blockers. The antiarrhythmic effects of
AH-1058 did not correlate with its plasma concentrations when administered either intravenously or orally. These results suggest that
AH-1058 can become a long-acting Ca(2+) channel blocker with unique antiarrhythmic properties, and that
AH-1058 may be used in certain
pathological processes, for which selective inhibition of the cardiac Ca(2+) channels is essential.