Central pre‐ and postsynaptic monoamine receptors in antidepressant therapy

Abstract

Activation of postsynaptic noradrenergic al-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 u,-receptor blocking capacity. The presynaptic u2-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 a*-receptors, a phenomenon which can even cause activation of brain NE neurons and form a basis for their therapeutic action. &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 Bz-receptor agonist. A reduced central B-receptor activation may, accordingly, contribute to depressive symptoms associated with treatment with Badrenoceptor 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.

The Effect of Sympathetic Antagonists on the Antidepressant Action of Alprazolam

“…This indicates that ǃ2 stimulation produces antidepressant effect. Reduced central ǃ-receptor activation may contribute to depressive symptoms associated with ǃ-adrenergic blocking drugs [71]. In the forced swimming test, it was found that isoprenaline increases the duration of immobility, while salbutamol decreases it [72].…”

The Effect of Sympathetic Antagonists on the Antidepressant Action of Alprazolam

“…This indicates that β2 stimulation produces antidepressant effect. Reduced central β-receptor activation may contribute to depressive symptoms associated with β-adrenergic blocking drugs [71]. In the forced swimming test, it was found that isoprenaline increases the duration of immobility, while salbutamol decreases it [72].…”

Dibenzoazepine analogues: the electrophysiological properties of JL3, a potential atypical antidepressant

“…As concerns locus coeruleus neurons, presynaptic c~2-adrenoceptors probably mediate the feedback inhibition seen after acute administration of tricyclic antidepressants (Svensson et al, 1981). However, somatodendritic 5-HT 1 autoreceptors could mediate the feedback inhibition of dorsal raphe neurons (Blier and De Montigny, 1994).…”