Jpn. J. Pharmacol. 69, 277-279 (1995)

A Xanthine Derivative Denbufylline Inhibits Negative Inotropic Response to Verapamil in Guinea Pig Ventricular Papillary Muscles, Independent of Its Phosphodiesterase Inhibitory Activity

Fujiko Sanae (1), Shinji Ohmae (1), Kenzo Takagi (2) and Ken-ichi Miyamoto (1,*)

(1) Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-11, Japan
(2) Second Department of Internal Medicine, Nagoya University School of Medicine, Tsurumai, Nagoya 466, Japan
(*) To whom correspondence should be addressed./I>

Abstract: A phosphodiesterase (PDE) III inhibitor, amrinone, inhibited both the negative inotropic actions of verapamil and nicardipine in guinea pig ventricular papillary muscle; this effect was canceled by the protein kinase A inhibitor H-89. The PDE IV inhibitor 1,3-di-n-butyl-7-(2'-oxopropyl)xanthine (denbufylline), which elicited a negative inotropic action by itself, attenuated the action of verapamil up to 10 microM, without any interaction with nicardipine. The attenuation by denbufylline was not influenced by H-89. This suggests that in the ventricular papillary muscle, denbufylline acts on some verapamil-sensitive site(s) in the membrane and interferes with the calcium channel function without involvement of its PDE inhibitory activity.

Keywords: Denbufylline, Negative inotropy, Calcium channel

Copyright© The Japanese Pharmacological Society 1995

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