Effects of HNS-32, a Novel Antiarrhythmic Agent, on Guinea-Pig Myocardium

Abstract

The electrophysiological and mechanical effects of HNS-32, a novel azulene-1-carboxamidine derivative with antiarrhythmic activity, were studied in isolated guinea-pig myocardial preparations. HNS-32 (10^–6–10^–4 mol/l) concentration-dependently decreased the maximum rate of rise (V_max) of action potential in isolated papillary muscle; the potency was the same or slightly higher than that of disopyramide. At 10^–4 mol/l, HNS-32 also shortened the action potential duration (APD) and depolarized the resting membrane potential; these effects were similar to those of 10^–5 mol/l verapamil. HNS-32 (10^–7–10^–4 mol/l), as well as verapamil (10^–8–10^–5 mol/l) and disopyramide (10^–6–10^–3 mol/l), had concentration-dependent negative chronotropic and negative inotropic effects on isolated right atrial and right ventricular papillary muscle preparations, respectively. The concentration-response relationship for the positive chronotropic effect of isoproterenol was not affected by HNS-32 (10^–5 mol/l). In isolated ventricular myocytes, HNS-32 (10^–6–10^–4 mol/l) concentration-dependently inhibited the peak amplitude of the L-type Ca²⁺ current. These results suggest that NHS-32 has V_max reducing activity on myocardial tissue, which may be responsible for antiarrhythmic effect. The drug may also have additional effect on the Ca²⁺ channel at higher concentrations.