Differences in presynaptic alpha-blockade, noradrenaline uptake inhibition, and potential antidepressant activity between (+)- and (-)mianserin.
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 alpha-adrenolytic effect. Evaluation of the effects of the enantiomers (+)(S)mianserin and (-)(R)mianserin showed that the alpha-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.
D000317:Adrenergic alpha-Antagonists; D000374:Aggression / Q000187:drug effects; D000818:Animals; D000928:Antidepressive Agents; D002540:Cerebral Cortex / Q000378:metabolism; D003984:Dibenzazepines / Q000494:pharmacology*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008803:Mianserin / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism; D013574:Synaptosomes / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D000928:Antidepressive Agents; D003984:Dibenzazepines; D008803:Mianserin; D009638:Norepinephrine