Methylated and demethylated tricyclic antidepressants and their binding to cell membranes.

We studied the binding of methylated and demethylated tricyclic antidepressants (TCA) to synaptic plasma brain membranes (SPM) and to lymphocyte, platelet and erythrocyte membranes. In the synaptic plasma membranes, more demethylated than methylated dibenzazepine derivatives were bound and the binding affinity was decreased. By contrast, in lymphocyte and platelet membranes more methylated derivatives were bound. Phosphatidylserine (PS) enhanced significantly the binding of methylated TCA in SPM without changing the dissociation constant (Kd). Lysophosphatidylserine did not affect the binding. PS also caused an increase of 3H-imipramine binding to lymphocyte membranes but the binding to platelet membranes was not affected. PS also enhanced 3H-5-HT uptake into platelets and 3H-noradrenaline uptake into lymphocytes.