Valdoxan, the first melatonergic antidepressant, presents an innovative receptor profile and mode of action. Valdoxan is a melatonergic agonist (MT₁ and MT₂ receptors) and 5-HT_2C antagonist. Valdoxan resynchronizes circadian rhythms in animal models of circadian rhythm disruption.

Innovative receptor profile of Valdoxan

Valdoxan is the first melatonergic antidepressant.

Valdoxan is a melatonergic agonist (MT₁ and MT₂ receptors) and 5-HT_2C antagonist. Binding studies indicate that Valdoxan has no effect on monoamine uptake and no affinity for α, β-adrenergic, histaminergic, cholinergic, dopaminergic and benzodiazepine receptors.

Valdoxan resynchronizes circadian rhythms in animal models of circadian rhythm disruption. Valdoxan increases noradrenaline and dopamine release specifically in the frontal cortex and has no influence on the extracellular levels of serotonin.

Valdoxan has shown an antidepressant effect in animal models of depression (learned helplessness test, despair test, chronic mild stress) as well as in models with circadian rhythm desynchronisation and in models related to stress and anxiety.

In humans, Valdoxan has positive phase shifting properties; it induces a phase advance of sleep, body temperature decline and melatonin onset.