The pharmacology of alpha receptors.

Norepinephrine (NE) and epinephrine act on alpha and beta adrenergic cell surface receptor molecules in many tissues. Molecular structure analysis has identified two families of alpha receptors, the alpha1A,B,C and the alpha2A,B,C,D families. These receptors are coupled to G proteins and alter cell activity through various second messenger systems to give catecholamines a broad range of response. Alpha1 adrenergic receptors are located on postsynaptic cells in smooth muscle, heart, vas deferens and brain. Major pharmacologic agonists include methoxamine and phenylephrine and antagonists are prazosin, phentolamine, and corynanthine. Most alpha receptors mediate activation of phospholipase C with generation of inositol trisphsosphate and diacylglycerol. Alpha2 receptors have diverse functions as they can act as autoreceptors to inhibit NE release in postganglionic nerve terminals or in the brain where they inhibit systemic sympathetic outflow. The postsynaptic alpha2 receptors are activated by clonidine and inhibited by yohimbine and rauwolscine. Following stimulation of alpha receptors, they rapidly desensitize and decrease their response to further stimulation. Drugs that selectively block the alpha1 adrenergic system cause vasodilatation through relaxation of vascular smooth muscle without reflex stimulation of cardiac function because the prejunctional alpha2 receptors remain unblocked. The blood pressure response to alpha1 receptor blockade is highly proportional to that component of vascular resistance maintained by sympathetic activation. A favorable hemodynamic effect of alpha blockers is seen with exercise where cardiac performance and blood flow are better maintained than with beta blockers. The most widely used alpha blockers are the alpha1 selective agents prazosin, doxazosin, and terazosin. When used as monotherapy, these agents lower diastolic pressures to 90 mm Hg or below in 70% of patients.