Alinidine antagonizes the myocardial effects of adenosine

Abstract

The bradycardiac drug alinidine (2.8–182.3 μM) antagonized the negative inotropic effect of adenosine in isolated left rat atria in a non-competitive fashion. A 50% reduction of the maximal adenosine effect was achieved with 64.6 μM alinidine. The shortening of the action potential duration and the suppression of slow action potentials in guinea pig atria by 1–10 μM adenosine could be abolished by 5.7 μM alinidine. Adenosine (1 mM) exerted a negative inotropic effect on isolated strips from the right ventricle of rat heart exposed to 0.36 μM isoproterenol, an effect which was fully antagonized by 91.1 μM alinidine. Addition of 1 mM adenosine to spontaneously beating isolated rat atria induced pronounced bradycardia. Under these conditions, the bradycardiac agent alinidine increased the contractile rate concentration dependently (11.4–182.3 μM), while the chemically unrelated bradycardiac compound UL-FS 49 did not accelerate the beat frequency. As alinidine antagonized all the cardiac actions of adenosine that we tested, it may be concluded that the drug interferes with A 1-receptor-mediated effects.