Pharmacology of antihypertensive agents with multiple actions.
Compounds with two or more different pharmacodynamic activities in a single molecule are designated as hybrid drugs. If several stereoisomers with different pharmacodynamic activities exist in one molecule, the term pseudo-hybrid drug is applied. In the treatment of hypertension, the use of hybrid drugs enables a considerable reduction in the number of tablets to be taken per day. Conversely, the dose of each individual component cannot be tritrated. Most hybrid drugs used in antihypertensive treatment are beta-blockers with an additional vasodilator component, caused by different mechanisms such as alpha-adrenoceptor blockade, beta 2-adrenoceptor agonism, ACE inhibition or direct relaxation of vascular smooth muscle. Examples include labetalol (in fact, a mixture of four stereoisomers), carvedilol, celiprolol, dilevalol, tertatolol and BWA-575 C. A combination of beta-receptor blockade and vasodilation may be beneficial from a hemodynamic point of view. More recently it has been recognized that urapidil and ketanserin are hybrid drugs, each containing at least two pharmacodynamic activities in their molecules.
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
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van Zwieten
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D006801:Humans
D000959:Antihypertensive Agents