Comparative study of the effects of mianserin, a tetracyclic antidepressant, and of imipramine on uptake and release of neurotransmitters in synaptosomes

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Abstract
The effects of mianserin, a tetracyclic antidepressant, on uptake and release of [3H]noradrena‐line (3H‐NA), [3H]dopamine (3H‐DA), [3H]‐5‐hydroxytryptamine(3H‐5‐HT) and [3H]γ‐aminobutyric 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 of tricyclic antidepressants with the neurotransmitter transport mechanisms at the presynaptic level.