title: 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 Ca2+ uptake by mianserin. Synaptosomes from rat hippocampus were incubated with 45Ca2+ in either resting or depolarizing (60 mM K+) choline medium, in the absence or presence (0.6-200 microM) of a mianserin enantiomer. The enantiomers were equipotent (IC50 approximating 50 microM) at inhibiting net depolarization-induced Ca2+ 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.
authors.affiliation: Département de Pharmacologie, Université de Montréal, Québec, Canada. lavoiepi@pharmco.umontreal.ca
authors.forename: P A
authors.initials: PA
authors.lastname: Lavoie
authors.forename: S
authors.initials: S
authors.lastname: Cherradi
authors.forename: R
authors.initials: R
authors.lastname: Elie
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002794:Choline; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008803:Mianserin / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D011188:Potassium / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015220:Calcium Channels; D008803:Mianserin; D002794:Choline; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine