Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein.
alpha 1-Receptor antagonists and antidepressant agents are basic (cationic) drugs that are known to bind to alpha 1-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, alpha 1-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 greater than prazosin greater than doxazosin greater than propranolol greater than doxepin = amoxapine = trimazosin = amitriptyline greater than imipramine greater than nortriptyline = desipramine = nomifensine greater than bupropion = maprotiline. [3H]lmipramine binding from AAG was displaced with the following potency order: prazosin greater than imipramine greater than propranolol greater than doxazosin greater than nortriptyline greater than desipramine greater than trimazosin. Tricyclic antidepressants produced similar degrees of displacement of both [3H]imipramine and [3H]prazosin from AAG; whereas, alpha 1-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.
Ferry
D G
DG
Caplan
N B
NB
Cubeddu
L X
LX
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000378:metabolism / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D002853:Chromatography, Liquid; D003956:Dialysis; D004347:Drug Interactions; D006801:Humans; D007099:Imipramine / Q000378:metabolism; D009961:Orosomucoid / Q000378:metabolism*; D011224:Prazosin / Q000378:metabolism; D011485:Protein Binding
D000317:Adrenergic alpha-Antagonists; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D009961:Orosomucoid; D007099:Imipramine; D011224:Prazosin