An overview of the pharmacodynamic properties and therapeutic potential of combined alpha- and beta-adrenoceptor antagonists.
Haemodynamically, the combination of alpha 1- and beta-adrenoceptor antagonists is a logical one. alpha 1-Adrenoceptor blockade causes vasodilatation and hence counteracts elevated peripheral vascular resistance, the most consistent haemodynamic derangement in established essential hypertension. beta-Blockers, which lower elevated blood pressure by a different (not yet clearly understood) mechanism, suppress the reflex tachycardia triggered by vasodilatation. Combined alpha/beta-adrenoceptor blockade can be obtained by the simultaneous administration of both types of adrenoceptor antagonists, but also by giving drugs that possess alpha- and beta-adrenoceptor antagonistic activity in the same molecule. Carvedilol and labetalol are the best known examples of such combined alpha/beta-adrenoceptor antagonists, although their pharmacodynamic profile is a result of different receptor selectivity of their component stereoisomers, rather than combined alpha/beta-blocking activity in a single chemical entity. Both compounds have been investigated clinically in the treatment of essential hypertension in moderate-to-large scale trials. A few newer combined alpha/beta-adrenoceptor antagonists, such as amosulalol, arotinolol and medroxalol have been developed, but clinical data on these compounds are relatively scarce.
van Zwieten
P A
PA
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy; D000077261:Carvedilol; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007741:Labetalol / Q000494:pharmacology / Q000627:therapeutic use; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D007741:Labetalol