[Ca(2+)-channel blockers and binding of tricyclic antidepressive agents].
The interactions between Ca(2+)-channel blockers (verapamil and gallopamil) and synaptic plasma membranes (SPM) from bovine brain or human lymphocyte and platelet plasma membranes were studied. Changes in binding parameters of [3H]imipramine, [3H]desmethylimipramine and [3H]gallopamil were determined after addition of unlabelled verapamil or imipramine and after addition of phosphatidylserine (PS) (PS-stimulation). Specific binding of [3H]imipramine to SPM was decreased and [3H]desmethylimipramine binding was increased by 1 microM verapamil. [3H]gallopamil binds specifically to SPM as well as to platelet and lymphocyte membranes. [3H]gallopamil binding to SPM or lymphocyte plasma membranes was PS-stimulated in contrast to platelet plasma membranes without PS effect on binding. Imipramine inhibited both [3H]gallopamil binding and PS-stimulated [3H]gallopamil binding to SPM or lymphocyte plasma membranes. Mutual effects of tricyclic antidepressants and Ca(2+)-channel blockers on their binding sites require relatively high drug concentrations. Mechanism of Ca(2+)-channel blockers action in the treatment of depression may be connected rather with changes in signal transduction through serotonin and catecholamine receptor systems than with direct interaction of drugs with binding sites for tricyclic antidepressants.
Krulík
R
R
Výzkumná psychiatrická laborator, 1. LF UK, Praha.
Bures
P
P
Fisar
Z
Z
Fuksová
K
K
Sikora
J
J
Beitlová
D
D
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D003891:Desipramine / Q000378:metabolism; D005711:Gallopamil / Q000494:pharmacology*; D006801:Humans; D007099:Imipramine / Q000378:metabolism; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000378:metabolism; D010718:Phosphatidylserines / Q000494:pharmacology; D013570:Synaptic Membranes / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
D000929:Antidepressive Agents, Tricyclic; D002121:Calcium Channel Blockers; D010718:Phosphatidylserines; D005711:Gallopamil; D014700:Verapamil; D007099:Imipramine; D003891:Desipramine