Differences in presynaptic ?-blockade, noradrenaline uptake inhibition, and potential antidepressant activity between (+)- and (-)mianserin

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Abstract
The effect of racemic mianserin on K+-evoked tritium release from rat brain cortex slices previously incubated with 3H-l-noradrenaline was studied. Racemic mianserin (10-9-10-5 M) increased stimulation-induced release dose-dependently. As methysergide, metiamide, and cyproheptadine failed to do so, it was concluded that this effect was probably not caused by the antihistamine or antiserotonin activity of racemic mianserin, but due to its α-adrenolytic effect. Evaluation of the effects of the enantiomers (+)(S)mianserin and (-)(R)mianserin showed that the α-adrenolytic effect resided in the (+)isomer, whereas the (-)isomer was inactive at a concentration of 10-6 M. Inhibition of noradrenaline into rat hypothalamic synaptosomes also showed stereospecificity in that (+)mianserin was about 300-times more active than (-)mianserin. Inhibition of rat muricidal behavior, a test for potential antidepressant activity, showed a similar dissociation in the effects of the two enantiomers, in that (+)mianserin was active, whereas (-)mianserin was not.