Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein.

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Ferry DG, Caplan NB, Cubeddu LX

Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein.

J Pharm Sci. 1986 Feb;75(2):146-9. doi: 10.1002/jps.2600750208.

PubMed ID

2870173 [ View in PubMed

]

Abstract

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.

DrugBank Data that Cites this Article

Drugs

Doxazosin

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Nortriptyline	Alpha-1A adrenergic receptor	Protein	Humans	No	Antagonist	Details

Drug Carriers

Drug	Carrier	Kind	Organism	Pharmacological Action	Actions
Amitriptyline	Alpha-1-acid glycoprotein 1	Protein	Humans	No	Binder	Details
Amoxapine	Alpha-1-acid glycoprotein 1	Protein	Humans	No	Not Available	Details
Bupropion	Alpha-1-acid glycoprotein 1	Protein	Humans	No	Antagonist	Details
Desipramine	Alpha-1-acid glycoprotein 1	Protein	Humans	No	Not Available	Details
Imipramine	Alpha-1-acid glycoprotein 1	Protein	Humans	No	Not Available	Details
Maprotiline	Alpha-1-acid glycoprotein 1	Protein	Humans	No	Not Available	Details
Nomifensine	Alpha-1-acid glycoprotein 1	Protein	Humans	No	Not Available	Details
Nortriptyline	Alpha-1-acid glycoprotein 1	Protein	Humans	No	Binder	Details
Prazosin	Alpha-1-acid glycoprotein 1	Protein	Humans	No	Substrate	Details
Propranolol	Alpha-1-acid glycoprotein 1	Protein	Humans	No	Not Available	Details

Drug Interactions

Drugs	Interaction
Integrate drug-drug interactions in your software
Bromocriptine Protriptyline	Protriptyline may increase the vasopressor activities of Bromocriptine.
Bromocriptine Amineptine	Amineptine may increase the vasopressor activities of Bromocriptine.
Bromocriptine Dimetacrine	Dimetacrine may increase the vasopressor activities of Bromocriptine.
Bromocriptine Butriptyline	Butriptyline may increase the vasopressor activities of Bromocriptine.
Bromocriptine Dosulepin	Dosulepin may increase the vasopressor activities of Bromocriptine.