ABSENCE OF STEREOSELECTIVITY OF SOME TRICYCLIC ANTIDEPRESSANTS FOR THE INHIBITION OF DEPOLARIZATION-INDUCED CALCIUM-UPTAKE IN RAT CINGULATECORTEX SYNAPTOSOMES

This study was conducted in order to investigate the inhibition of syn aptosomal calcium-45 uptake by oxaprotiline, trimipramine and doxepin stereoisomers in the rat cingulate cortex which is an associative area of the cortex that interacts with the limbic system. A concentration- dependent inhibition of net depolarization-induced calcium-45 uptake w as observed for all substances tested. No significant difference in po tency could be established within any of the pairs of antipodes and th e IC50 values obtained were in the 30 muM to 50 muM range. These resul ts are quite similar to those previously obtained with this group of c ompounds in hippocampal synaptosomes where discrepancies between relat ive calcium channel antagonism and clinical activity of the antipodes have been identified. Therefore, the present study of stereoisomers of tricyclic antidepressants fails to resolve these discrepancies and do es not provide unequivocal support for the hypothesis that calcium cha nnel blockade is somehow responsible for the therapeutic effect of tri cyclic antidepressants.