2001 Volume 63 Issue 2 Pages 135-143
The inotropic effect of diazepam, a benzodiazepine derivative, and its mechanism of action were examined using guinea pig heart and single ventricular cell preparations. In Langendorff hearts and right ventricular free-wall preparations, diazepam (10 to 100 μM) produced a monophasic negative inotropic effect in a concentration dependent manner. Neither a central type (flumazenil 1 μM) nor a peripheral type (PK11195 10 μM) of benzodiazepine receptor antagonist antagonized the monophasic negative inotropic effects of diazepam. Diazepam (10 to 100 μM) shortened action potential duration of papillary muscle in a concentration dependent manner. In isolated single ventricular cells, diazepam (30 and 100 μM) inhibited the calcium current (ICa) in a concentration dependent manner. Diazepam produced a significant decrease in ICa elicited by first depolarizing pulses, however, the decrease of ICa was not augmented during a train of depolarizing pulses. Thus, diazepam appears to produce a tonic block of cardiac calcium channels and the mode of inhibition is clearly different from the use-dependent block of verapamil. From these results, it was concluded that diazepam produces a monophasic negative inotropic effect that is independent of the benzodiazepine receptor, and is probably mediated through an inhibition of ICa in guinea pig heart preparations.
Journal of The Japanese Society of Veterinary Science
