Absence of stereoselectivity of some tricyclic antidepressants for the inhibition of depolarization-induced calcium uptake in rat cingulate cortex synaptosomes.
This study was conducted in order to investigate the inhibition of synaptosomal 45calcium 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 45calcium uptake was observed for all substances tested. No significant difference in potency could be established within any of the pairs of antipodes and the IC50 values obtained were in the 30 microM to 50 microM range. These results are quite similar to those previously obtained with this group of compounds in hippocampal synaptosomes where discrepancies between relative 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 does not provide unequivocal support for the hypothesis that calcium channel blockade is somehow responsible for the therapeutic effect of tricyclic antidepressants.
Lavoie
P A
PA
Department of Pharmacology, University of Montreal, Quebec.
Beauchamp
G
G
Elie
R
R
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D046508:Culture Techniques; D006179:Gyrus Cinguli / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013574:Synaptosomes / Q000187:drug effects*
D000929:Antidepressive Agents, Tricyclic; D015220:Calcium Channels; D002118:Calcium