ATC Group: N06AX Other antidepressants

Agomelatine is a melatonergic agonist (MT1 and MT2 receptors) and 5-HT2C antagonist. In humans, agomelatine has positive phase shifting properties; it induces a phase advance of sleep, body temperature decline and melatonin onset.

Bupropion is a selective inhibitor of the neuronal re-uptake of catecholamines (noradrenaline and dopamine) with minimal effect on the re-uptake of indolamines (serotonin) and does not inhibit either monoamine oxidase. The mechanism by which bupropion enhances the ability of patients to abstain from smoking is unknown. However, it is presumed that this action is mediated by noradrenergic and/or dopaminergic mechanisms.

Duloxetine is a combined serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor. It weakly inhibits dopamine reuptake with no significant affinity for histaminergic, dopaminergic, cholinergic and adrenergic receptors.

The mechanism of the antidepressant effect of gepirone is not fully understood but is thought to be related to its modulation of serotonergic activity in the CNS through selective agonist activity at 5HT1A receptors. The pharmacological activity of gepirone is attributed to the parent drug and its major metabolites 3'-OH-gepirone and 1-PP. Gepirone and its 3'-OH metabolite bind to 5HT1A receptors (Ki = 38 nM and 58 nM, respectively), where they act as agonists, while the 1-PP metabolite binds to alpha2 receptors (Ki = 42 nM).

Mianserin is a tetracyclic antidepressant. It does not appear to have significant anti-cholinergic properties, but has a marked sedative action. Unlike amitriptyline, it does not prevent the peripheral re-uptake of noradrenaline; it blocks presynaptic alpha-adrenoceptors and increases the turnover of brain noradrenaline.

Milnacipran is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the management of fibromyalgia in patients that are 18 years old or above.

Mirtazapine is a centrally active presynaptic α₂-antagonist, which increases central noradrenergic and serotonergic neurotransmission. The enhancement of serotonergic neurotransmission is specifically mediated via 5-HT₁ receptors, because 5-HT₂ and 5-HT₃ receptors are blocked by mirtazapine. Both enantiomers of mirtazapine are presumed to contribute to the antidepressant activity, the S(+) enantiomer by blocking α₂ and 5-HT₂ receptors and the R(-) enantiomer by blocking 5-HT₃ receptors.

Nefazodone is a synthetically derived phenylpiperazine antidepressant. The mechanism of action of nefazodone, as with other antidepressants, is unknown. Preclinical studies have shown that nefazodone inhibits neuronal uptake of serotonin and norepinephrine.

Reboxetine is a highly selective and potent inhibitor of noradrenaline reuptake. Noradrenaline reuptake inhibition and the consequent increase of noradrenaline availability in the synaptic cleft and modification of noradrenergic transmission, reportedly is among the most relevant mechanisms of action of known antidepressant drugs.

Tianeptine is an antidepressant. In man, tianeptine is characterised by marked action on somatic complaints, especially gastrointestinal complaints related to anxiety and mood disturbances. Moreover, tianeptine has no effect on sleep and alertness nor on the cholinergic system (no anticholinergic symptoms).

Trazodone is a potent antidepressant. It also has anxiety reducing activity. Trazodone is a triazolopyridine derivative chemically unrelated to known tricyclic, tetracyclic and other antidepressant agents. It has negligible effect on noradrenaline re-uptake mechanisms.

Venlafaxine has an antidepressant effect. The mechanism of its action in humans is believed to be associated with its potentiation of neurotransmitter activity in the central nervous system.

Vilazodone is a selective serotonin reuptake inhibitor and a 5HT_1A receptor partial agonist. It is used for the treatment of major depressive disorder (MDD) in adults. The mechanism of action of vilazodone in the treatment of major depressive disorder is not fully understood, but is thought to be related to its enhancement of serotonergic activity in the CNS through selective inhibition of serotonin reuptake.

Vortioxetine is a 5-HT₃, 5-HT₇, and 5-HT_1D receptor antagonist, 5-HT_1B receptor partial agonist, 5-HT_1A receptor agonist and inhibitor of the 5-HT transporter, leading to modulation of neurotransmission in several systems, including predominantly the serotonin but probably also the norepinephrine, dopamine, histamine, acetylcholine, GABA and glutamate systems. This multimodal activity is considered responsible for the antidepressant and anxiolytic-like effects and the improvement of cognitive function, learning and memory observed with vortioxetine in animal studies.