ASPECTS ON THE BETA-1-ADRENOCEPTOR STIMULATORY MECHANISM OF PRENALTEROL

Publisher Summary Prenalterol ((-)-H 80/62, H 133/22) has previously been characterized as a selective beta-1-adrenoceptor agonist with about 80% intrinsic activity of that of isoprenaline on heart rate and cardiac contractility in the anaesthetized cat. For a further characterization of the interaction of prenalterol with beta-adrenoceptors, its effects have been compared with those of isoprenaline and procaterol (OPC 2009) on contractility in cat heart and on subtetanic contractions in soleus muscle in vitro and on beta-adrenoceptor binding and adenylate cyclase activity in those tissues. This chapter discusses various aspects on the beta-1-adrenoceptor stimulatory mechanism of prenalterol based on this study. Prenalterol binds to both beta-1- and beta-2-adrenoceptors with equal affinity. The cardio-selective effect of prenalterol is caused by the fact that prenalterol has intrinsic stimulatory activity only on beta-1-adrenoceptors. Alpha-adrenoceptors do not seem to be involved in the positive inotropic response induced by prenalterol. The cardiac inotropic effect of prenalterol is achieved at low, if any, increase of adenylate cyclase activity. This finding may indicate that there is a large receptor and adenylate cyclase activity reserve for full agonists in the cardiac muscle. Consequently, a marginal increase in the adenylate cyclase activity might be sufficient to achieve the maximal contractility effect of prenalterol. The lack of adenylate cyclase activation might also be because of the fact that the inotropic response of a beta-1-adrenoceptor partial agonist such as prenalterol is not mediated via cyclic adenosine monophosphate (AMP).