Inhibition of K+-induced Ca2+ uptake in rat hippocampus synaptosomes by mianserin enantiomers

Abstract In order to test potential links with other stereospecific neurobiological effects of mianserin, the present study explored the stereospecificity for inhibition of depolarization-induced Ca 2+ uptake by mianserin. Synaptosomes from rat hippocampus were incubated with 45 Ca 2+ in either resting or depolarizing (60 mM K + ) choline medium, in the absence or presence (0.6–200 μM) of a mianserin enantiomer. The enantiomers were equipotent (IC 50 approximating 50 μM) at inhibiting net depolarization-induced Ca 2+ uptake. This finding, therefore, cannot help to explain the stereoselective enhancement of noradrenaline release by S (+)-mianserin; it is also not in keeping with the stereospecificity exhibited by mianserin in acute tests predictive of antidepressant activity, thus suggesting that the calcium-channel blocking activity of mianserin is not linked to its antidepressant effect.