Ilse Streller

Alinidine antagonizes the myocardial effects of adenosine

The bradycardiac drug alinidine (2.8-182.3 microM) 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 microM alinidine. The shortening of the action potential duration and the suppression of slow action potentials in guinea pig atria by 1-10 microM adenosine could be abolished by 5.7 microM alinidine. Adenosine (1 mM) exerted a negative inotropic effect on isolated strips from the right ventricle of rat heart exposed to 0.36 microM isoproterenol, an effect which was fully antagonized by 91.1 microM 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 microM), 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 A1-receptor-mediated effects.

PHARMACOLOGICAL INFLUENCES ON PRE- AND POSTSYNAPTIC α-ADRENERGIC RECEPTORS

The effects of α-adrenolytic agents on BP, HR and neural sympathetic activity after intracisternal injection in anaesthetized animals have been compared with their effects on pre- and postsynaptic α-receptors in rat vas deferens. - It is concluded that α-adrenolytic agents with prevalent “presynaptic” activity reduce BP by inhibiting the negative feed-back mechanism of NE-liberation. The resulting surplus of NE then stimulates postsynaptic α-receptors.