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

In order to test potential links with other stereospecific neurobiological effects of mianserin, the present study explored the stereospecificity for inhibition of depolarization-induced Ca2+ uptake by mianserin. Synaptosomes from rat hippocampus were incubated with Ca-45(2+) in either resting or de polarizing (60 mM K+) choline medium, in the absence or presence (0.6-200 m u M) of a mianserin enantiomer. The enantiomers were equipotent (IC50 appro ximating 50 mu M) at inhibiting net depolarization-induced Ca2+ uptake. Thi s finding, therefore, cannot help to explain the stereoselective enhancemen t of noradrenaline release by S(+)-mianserin; it is also not in keeping wit h 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. (C) 1999 Elsevier Science B.V. All rights reserved.