Antihypertensive drugs interacting with alpha- and beta-adrenoceptors. A review of basic pharmacology

Antihypertensive activity can be induced by the following types of drugs: alpha-adrenoceptor antagonists; beta-adrenoceptor antagonists (beta-blockers); and alpha 2-adrenoceptor agonists (in the central nervous system). After a general survey of peripheral and central alpha- and beta-adrenoceptors, including their modern classification and subdivision, attention was paid to the various drugs with antihypertensive activity based upon interaction with various alpha- and beta-adrenoceptors. Of the peripheral alpha-adrenoceptor blockers, only those selective for alpha 1-adrenoceptors are useful antihypertensives. Prazosin and its successors (doxazosin, terazosin, trimazosin) are the best-known examples of such drugs. Their mode of action, and the low incidence and degree of reflex tachycardia, can be satisfactorily explained on the basis of alpha 1-adrenoceptor blockade in the periphery and possibly also in the CNS. Urapidil is a selective alpha 1-adrenoceptor blocker with an additional central component not based upon interaction with alpha-adrenoceptors. With respect to centrally acting alpha 2-adrenoceptor agonists, clonidine, guanfacine and alpha-methyldopa are the prototypes. Their antihypertensive activity is triggered by the stimulation of central alpha 2-adrenoceptors in the brain stem, causing reduced peripheral sympathetic activity and hence a fall in blood pressure and heart rate. Sedation, a common side effect of these drugs, is assumed to be mediated by alpha 2-adrenoceptors at cortical sites. Although beta-adrenoceptor blocking agents (beta-blockers) are widely and successfully used as antihypertensives, their mode of action is still poorly understood, only hypotheses being available at present. However, their side effects can be rationally explained on the basis of beta-adrenoceptor blockade.