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 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.
Lavoie
P A
PA
Département de Pharmacologie, Université de Montréal, Québec, Canada. lavoiepi@pharmco.umontreal.ca
Cherradi
S
S
Elie
R
R
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
D018687:Antidepressive Agents, Second-Generation; D015220:Calcium Channels; D008803:Mianserin; D002794:Choline; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine