Central pre‐ and postsynaptic monoamine receptors in antidepressant therapy

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Abstract
Activation of postsynaptic noradrenergic α1‐receptors may be involved in the mediation of psychomotor activating effects of tricyclic antidepressant (TCA) drugs. On the other hand, the pronounced sedative properties of some TCA drugs seem to be correlated with their α1‐receptor blocking capacity. The presynaptic α2‐receptors probably mediate the feed back inhibition of central NE neurons seen after administration of TCA drugs, particularly the secondary amines. Yet other antidepressants such as mianserin are potent antagonists at central α2‐receptors, a phenomenon which can even cause activation of brain NE neurons and form a basis for their therapeutic action. β‐Receptor activation in the brain is also suggested to participate in the therapeutic effect of several drugs, e.g. mianserin and the putative antidepressant agent salbutamol, a β2‐ receptor agonist. A reduced central β‐receptor activation may, accordingly, contribute to depressive symptoms associated with treatment with β‐adrenoceptor blocking drugs, both by their action per se as well as by secondary effects on the monoamine systems, which we recently have demonstrated. Facilitation of brain 5‐HT neurotransmission seems to be achieved with several TCA drugs not only via inhibition of reuptake but also through sensitization of postsynaptic 5‐HT receptors, developing during repeated treatment. In contrast the “presynaptic” 5‐HT receptors do not show increased sensitivity during chronic TCA drug treatment, thus allowing for an enhanced synaptic effect of 5‐HT induced by TCA drugs.

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