Effect of antidepressants on ATP-dependent calcium uptake by neuronal endoplasmic reticulum

Abstract

This study investigated the effect of tricyclic and atypical antidepressants on adenosine triphosphate (ATP) dependent calcium uptake by the endoplasmic reticulum of lysed synaptosomes from rat brain cortex. Tricyclic antidepressants (imipramine, desipramine, clomipramine, amitriptyline) exhibited no effect in the lower range (0.06 to 2 µM) of drug concentrations, and a concentration-dependent inhibition of calcium uptake in the upper range (6 to 200 µM). A concentration-dependent inhibition was observed for atypical antidepressants (mianserin, desmethylmianserin, venlafaxine, desmethylvenlafaxine, fluoxetine) in both the lower and the upper range of drug concentrations. Since no stimulation of calcium uptake was observed in either concentration range, it appears that the tricyclic and atypical antidepressants tested are not capable of normalizing, through their effect on the endoplasmic reticulum, an overactive calcium signal, which is possibly implicated in the etiology of affective disorders. Also, although only marginal inhibition of calcium uptake is expected at brain concentrations of tricyclics and mianserin–desmethylmianserin that are likely to be encountered during clinical use, a more substantial inhibition could occur with fluoxetine.Key words: adenosine triphosphate-dependent calcium uptake, neuronal endoplasmic reticulum, lysed brain synaptosomes, tricyclic antidepressants, atypical antidepressants.