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Blockade of presynaptic α-receptors and of amine uptake in the rat brain by the antidepressant mianserine

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Summary

Mianserine (Org GB 94, Tolvon®) is 1, 2, 3, 4, 10, 14b-hexahydro-2-methyl-dibenzo [c, f] pyrazino [1, 3-a] azepine hydrochloride, a new antidepressant drug. Its effect on noradrenaline release and its capacity to inhibit amine uptake were investigated. Mianserine increased the release of 3H-noradrenaline from field-stimulated cortical slices previously labelled with the tritiated transmitter. The assumption that this effect is due primarily to the blockade of the presynaptic noradrenergic α-receptors is supported by the fact that mianserine failed to augment 3H-noradrenaline release further after blockade of the presynaptic α-receptors by phentolamine. In the reciprocal experiment, phentolamine failed to augment 3H-noradrenaline release after exposure of the slices to mianserine. The hypothesis is further reinforced by the fact that mianserine antagonized the reduction of 3H-noradrenaline release by clonidine in the same manner as the α-blocking drugs phentolamine and phenoxybenzamine. Mianserine inhibited noradrenaline uptake in vitro and in vivo (in the rat heart and midbrain-diencephalon synaptosomes from pretreated rats.) Only a marginal inhibition of serotonin uptake was observed.

It therefore appears that mianserine increases the concentration of noradrenaline in the synaptic cleft by blocking the presynaptic α-receptors and inhibiting uptake. Whether or not this increase has functional consequences at postsynaptic noradrenergic receptor sites is unknown. It is possible, however, that postsynaptic receptor blockade counteracts the increase in available noradrenaline.

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Baumann, P.A., Maître, L. Blockade of presynaptic α-receptors and of amine uptake in the rat brain by the antidepressant mianserine. Naunyn-Schmiedeberg's Arch. Pharmacol. 300, 31–37 (1977). https://doi.org/10.1007/BF00505077

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  • DOI: https://doi.org/10.1007/BF00505077

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