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

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-l-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.