Pharmacologic aspects of cardioselectivity in a beta-blocking drug.

Beta 2 adrenoceptors have been subdivided into beta 1 and beta 2 receptors, both by the varying response of different tissues to sympathomimetic amines and, more recently, by radioligand-binding techniques. It would appear that beta 1 receptors occur predominantly in the heart, whereas beta 2 receptors are found in lungs, peripheral blood vessels and uterus, and are also involved with glycogenolysis and glucagon and insulin secretion. In addition, the distribution of beta 1 receptors appears to relate to the density of sympathetic innervation of an organ or tissue, but tissues without sympathetic innervation are found to contain beta 2 receptors. Thus, beta 1 adrenoceptors may be considered as physiologically innervated receptors mediating responses to neuronally released norepinephrine, and beta 2 receptors as mediating responses to circulating catecholamines, particularly epinephrine. Radioligand-binding studies have also shown that the heart contains beta 2 receptors and the lung beta 1 receptors, but these are in the minority, and their role has not been identified. For many years, cardioselective beta 1-adrenoceptor antagonists have been available. This was considered to be a dose-dependent phenomenon but recent evidence has cast doubt on the concept that cardioselectivity is lost during dose increases within the therapeutic range. Nevertheless, even small doses of cardioselective drugs may show some beta 2-receptor antagonism, and may have adverse effects on patients with obstructive airways disease. Finally, nonselective drugs may result in a diastolic pressor effect in the presence of circulating catecholamines in contrast to the "vascular sparing" seen with cardioselective drugs.