Jpn. J. Pharmacol. 71 (4), 333-335 (1996)

Negative Chronotropic and Inotropic Effects of U-92032, a Novel T-Type Ca2+ Channel Blocker, on the Isolated, Blood-Perfused Dog Atrium

Manoj Lakhe, Yasuyuki Furukawa (*), Takanori Yonezawa, Yoshito Nagashima, Masamichi Hirose and Shigetoshi Chiba

Department of Pharmacology, Shinshu University School of Medicine, Matsumoto 390, Japan (*) To whom correspondence should be addressed.

Abstract: We investigated the effects of U-92032 ((7-((bis-4-fluorophenyl)methyl)-1-piperazinyl)-2-2(2- hydroxyethylamino)-4-(1-methylethyl)-2,4,6-cycloheptatrien-1-one), a novel T-type Ca2+ channel blocker, on sinus rate and atrial contractile force in the isolated, blood-perfused atrium of the dog. U-92032 (1 to 300 nmol) induced negative chronotropic and inotropic responses in a dose-dependent manner, and the percentage decrease in sinus rate was less than that in atrial contractile force. Atropine did not affect the negative responses to U-92032. These results suggest that U-92032, a T-type Ca2+ channel blocker, simultaneously decreases the sinus rate and atrial force as do L-type Ca2+ channel blockers in the isolated dog atrium.

Keywords: U-92032, T-type Ca2+ channel, L-type Ca2+ channel

Copyright© The Japanese Pharmacological Society 1996

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