DIFFERENTIAL EFFECT OF DESIPRAMINE AND 2-HYDROXYDESIPRAMINE ON DEPOLARIZATION-INDUCED CALCIUM-UPTAKE IN SYNAPTOSOMES FROM RAT LIMBIC SITES

This study was conducted to investigate the inhibition of synaptosomal Ca-45 uptake by desipramine and its major metabolite 2-hydroxydesipramine in the rat hippocampus and cingulate cortex, areas associated with emotional control. A concentration-dependent inhibition of net depolarization-induced Ca-45 uptake was observed for desipramine (20-200 mu M) in synaptosomes from both sites. However, 20 mu M 2-hydroxydesipramine failed to inhibit calcium channel function in either of the two limbic sites; higher concentrations (60 or 200 mu M) did produce a minor degree of inhibition in hippocampus synaptosomes. Others have shown that the clinically encountered plasma concentrations of 2-hydroxydesipramine are lower than those of desipramine, and the brain concentration of 2-hydroxydesipramine is therefore not expected to surpass or even reach 20 mu M. In view of the previously observed clinical activity of 2-hydroxydesipramine, the present results indicate that calcium channel antagonism may not be the basis for the therapeutic effect of tricyclic antidepressants.