Tricyclic antidepressants and calcium channel blockers: interactions at the (-)-desmethoxyverapamil binding site and the serotonin transporter.
The activity of various calcium channel blockers at the serotonin transporter, as determined by their effects on imipramine binding and serotonin uptake, was investigated in rat brain and human platelets. In addition, the effect of tricyclic antidepressants on the binding of calcium channel blockers was evaluated. Verapamil was found to be a competitive inhibitor of both imipramine binding and serotonin uptake in brain and platelets. The inhibitory activity of verapamil was calcium-independent. Chronic verapamil treatment resulted in a significant decrease (28%) in [3H]imipramine binding in the rat hypothalamus but had no effect on [3H]imipramine binding to cerebral cortex membranes or on [3H]serotonin uptake in these two brain regions. Tricyclic antidepressants inhibited (-)-[3H]desmethoxyverapamil binding but did not affect [3H]nitrendipine binding to rat cerebral cortex membranes. Chronic imipramine treatment induced a non-significant increase (34%) in (-)-[3H]desmethoxyverapamil binding but did not alter [3H]nitrendipine binding in rat cerebral cortex. These interactions may be relevant to an understanding of the beneficial effects of verapamil in major affective disorders and may suggest an involvement of calcium channels in the pharmacological activity of tricyclic antidepressants.
Rehavi
M
M
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Carmi
R
R
Weizman
A
A
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels; D007099:Imipramine / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009568:Nitrendipine / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D014700:Verapamil / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011978:Receptors, Nicotinic; D011985:Receptors, Serotonin; D012701:Serotonin; C043184:4-desmethoxyverapamil; D009568:Nitrendipine; D014700:Verapamil; D007099:Imipramine