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- Title
Effects of HNS-32, a Novel Antiarrhythmic Agent, on Guinea-Pig Myocardium.
- Authors
Noguchi, Kazuo; Kase, Junya; Saitoh, Mariko; Masumiya, Haruko; Saitoh, Masaki; Nakazawa, Tomoo; Tanaka, Yoshio; Tanaka, Hikaru; Hashimoto, Keitaro; Shigenobu, Koki
- 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[sup –6] –10[sup –4] mol/l) concentration-dependently decreased the maximum rate of rise (V[sub max] ) of action potential in isolated papillary muscle; the potency was the same or slightly higher than that of disopyramide. At 10[sup –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[sup –5] mol/l verapamil. HNS-32 (10[sup –7] –10[sup –4] mol/l), as well as verapamil (10[sup –8] –10[sup –5] mol/l) and disopyramide (10[sup –6] –10[sup –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[sup –5] mol/l). In isolated ventricular myocytes, HNS-32 (10[sup –6] –10[sup –4] mol/l) concentration-dependently inhibited the peak amplitude of the L-type Ca[sup 2+] current. These results suggest that NHS-32 has V[sub max] reducing activity on myocardial tissue, which may be responsible for antiarrhythmic effect. The drug may also have additional effect on the Ca[sup 2+] channel at higher concentrations.Copyright © 2002 S. Karger AG, Basel
- Subjects
MYOCARDIAL depressants; GUINEA pigs; GUINEA pigs as laboratory animals; DISOPYRAMIDE; ISOPROTERENOL; CALCIUM antagonists
- Publication
Pharmacology, 2002, Vol 64, Issue 1, p36
- ISSN
0031-7012
- Publication type
Article
- DOI
10.1159/000056148