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

This study investigated the effect of tricyclic and atypical antidepressant s on adenosine triphosphate (ATP) dependent calcium uptake by the endoplasm ic reticulum of lysed synaptosomes from rat brain cortex. Tricyclic antidep ressants (imipramine, desipramine, clomipramine, amitriptyline) exhibited n o effect in the lower range (0.06 to 2 muM) of drug concentrations, and a c oncentration-dependent inhibition of calcium uptake in the upper range (6 t o 200 muM). A concentration-dependent inhibition was observed for atypical antidepressants (mianserin, desmethylmianserin, venlafaxine, desmethylvenla faxine, fluoxetine) in both the lower and the upper range of drug concentra tions. Since no stimulation of calcium uptake was observed in either concen tration range, it appears that the tricyclic and atypical antidepressants t ested are not capable of normalizing, through their effect on the endoplasm ic reticulum, an overactive calcium signal, which is possibly implicated in the etiology of affective disorders. Also, although only marginal inhibiti on of calcium uptake is expected at brain concentrations of tricyclics and mianserin-desmethylmianserin that are likely to be encountered during clini cal use, a more substantial inhibition could occur with fluoxetine.