| Autor: |
Noguchi, Kazuo, Kase, Junya, Saitoh, Mariko, Masumiya, Haruko, Saitoh, Masaki, Nakazawa, Tomoo, Tanaka, Yoshio, Tanaka, Hikaru, Hashimoto, Keitaro, Shigenobu, Koki |
| Předmět: |
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| Zdroj: |
Pharmacology; Jan2002, Vol. 64 Issue 1, p36-42, 7p, 2 Diagrams, 4 Graphs |
| Abstrakt: |
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 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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