Compounds capable of blocking a-adrenergic receptive regions by preventing various agonists from acting on them are called a-blockers.
The distinctive feature of a-adrenoblockers is their ability to reduce the pressor effect of pharmacological doses of epinephrine (adrenaline).
a1-Receptors act by phospholipase C activation, which, in turn, forms inositol trisphos-phate, which together with diacylglycerol, are second messenger molecules used in signal transduction in biological cells.
In blood vessels these cause vasoconstriction. Blood vessels with a1-receptors are present in the skin and the gastrointestinal system, and during the flight-or-fight response there is decreased blood flow to these organs. This is the reason people can appear pale when they have been frightened.
a2-Receptors act by inactivation of adenylate cyclase; cyclic AMP (adenosine-monophosphate) levels within the cell decrease.
In particular, postsynaptic a1-blockers act on the a-receptive regions located on the smooth muscle of blood vessels and counteract the pressor, vasoconstricting effect of epi-nephrine and norepinephrine. In addition, they exhibit a direct relaxant effect on smooth muscle, which leads to peripheral dilation of blood vessels, which in turn raises blood pressure. However, they also exhibit a cardiostimulatory effect, which is frequently a cause of tachycardia.
Presynaptic a2-receptive regions are located on sympathetic nerve endings, and their blockage, evidently by a mechanism of reversible binding, increases output of epinephrine from nerve endings. Such pharmacological action has extremely limited clinical use; however, it is a valuable laboratory instrument. The alkaloid yohimbin is a selective o^-adrenoblocker. Clinically useful o-blockers are:
1. Long-acting, noncompetitive antagonists (phenoxybenzamine), which form strong chemical bonds with o-receptor regions, can block o-receptors for days and even weeks.
2. Reversible competitive antagonists, nonselective (phentolamine, tolazoline), and arselectively acting (prazosin, terazosin) that reversibly and competitively block o-receptive regions; terazosin can last a few hours. At the same time, blockage of o-receptors can be interrupted and stopped by large doses of an agonist such as nor-epinephrine.
3. Ergot alkaloids (ergotamine, ergonovine) also exhibit certain nonselective o-adrenoblocking activity; however, they primarily exhibit spasmogenic action on smooth muscle, causing a constriction of blood vessels.
4. Selective c<2-adrenoblockers such as the alkaloid yohimbin have limited clinical use.
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