Abstract
α1-Receptor antagonists and antidepressant agents are basic (cationic) drugs that are known to bind to α1-acid glycoprotein (AAG). Since these drugs are frequently co-administered and since they bind to the same protein, this investigation was designed to evaluate the “in vitro” ability of antidepressants, α1-receptor antagonists, and propranolol to displace [3H]imipramine and [3H]prazosin from the AAG binding site(s). Equilibrium dialysis was employed. Of the drugs studied, the following order of potency in displacing [3H]prazosin was found: trazodone > prazosin > doxazosin > propranolol > doxepin = amoxapine = trimazosin = amitriptyline > imipramine > nortriptyline = desipramine = nomifensine > bupropion = maprotiline. [3H]lmipramine binding from AAG was displaced with the following potency order: prazosin > imipramine > propranolol > doxazosin > nortriptyline > desipramine > trimazosin. Tricyclic antidepressants produced similar degrees of displacement of both [3H]imipramine and [3H]prazosin from AAG; whereas, α1-receptor antagonists were more effective displacers of [3H]prazosin than of [3H]imipramine. Furthermore, the demethylated metabolites of imipramine and amitriptyline were less potent displacers than their parent compounds. These results suggest that more than a single binding site may be available for binding to AAG and that hydrophobic bonding is important in the binding of drugs to AAG.
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