Manoj Lakhe, Yasuyuki Furukawa (*), Takanori Yonezawa, Masamichi Hirose,
Yoshito Nagashima, Yusuke Miyashita and Shigetoshi Chiba
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
(*) To whom correspondence should be addressed.
Abstract: To investigate whether a Ca2+ sensitizer increases sinus rate, we studied the effects of racemic thiadiazinone, EMD 53998 (a Ca2+ sensitizer with phosphodiesterase inhibitory action) and its (+)-enantiomer BMD 57033 (a relatively pure Ca2+ sensitizer) on isolated, blood-perfused spontaneously beating right atria and paced left ventricles of the dogs. EMD 53998 increased sinus rate dose-dependently, but EMD 57033 did not. Both substances increased atrial and ventricular contractile force. Propranolol did not affect the responses to each substance. These results suggest that the Ca2+ sensitizing action induced by EMD 57033 does not affect pacemaker currents directly.
Keywords: EMD 57033, Ca2+ sensitizer, Sinus rate