Comparative study of the effects of mianserin, a tetracyclic antidepressant, and of imipramine on uptake and release of neurotransmitters in synaptosomes.
The effects of mianserin, a tetracyclic antidepressant, on uptake and release of [3H]noradrenaline (3H-NA), [3H]dopamine (3H-DA), [3H]-5-hydroxytryptamine(3H-5-HT) and [3H]gamma-amino-butyric acid (3H-GABA) in synaptosomes from different areas of the rat brain were investigated in a comparative study with the tricyclic antidepressant imipramine. Mianserin and imipramine were inhibitors of 3H-NA uptake in the hypothalamus, but could not increase 3H-NA release from noradrenergic nerve endings. This behaviour was similar to that of (+)-amphetamine. Both mianserin and imipramine had essentially no effect on 3H-DA transport mechanisms in striatal synaptosomes. (+)-Amphetamine, in contrast, strongly affected both 3H-DA uptake and release. Imipramine was stronger than mianserin in inhibiting 3H-5-HT accumulation by striatal synaptosomes. In contrast, mianserin stimulated 3H-5-HT release whereas imipramine was ineffective. Mianserin had virtually no inhibitory activity on 3H-5-HT uptake by rat blood platelets. Imipramine was a modest inhibitor of 3H-GABA accumulation by whole brain synaptosomes; mianserin had no effect. Both drugs did not alter 3H-GABA release. These results indicate that mianserin interferes in a way different from that to tricyclic antidepressants with the neurotransmitter transport mechanisms at the presynaptic level.
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D001921:Brain / Q000648:ultrastructure; D003864:Depression, Chemical; D003913:Dextroamphetamine / Q000494:pharmacology; D003984:Dibenzazepines / Q000494:pharmacology*; D007099:Imipramine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008803:Mianserin / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014439:Tyramine / Q000494:pharmacology
D003984:Dibenzazepines; D018377:Neurotransmitter Agents; D008803:Mianserin; D007099:Imipramine; D003913:Dextroamphetamine; D014439:Tyramine