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 Ca(2+) 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 Ca(2+) channel at higher concentrations.

journal_name

Pharmacology

journal_title

Pharmacology

authors

Noguchi K,Kase J,Saitoh M,Masumiya H,Saitoh M,Nakazawa T,Tanaka Y,Tanaka H,Hashimoto K,Shigenobu K

doi

10.1159/000056148

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

36-42

issue

1

eissn

0031-7012

issn

1423-0313

pii

pha64036

journal_volume

64

pub_type

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