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Amisulpride is approved for clinical use in treating schizophrenia in a number of European countries and also for treating dysthymia, a mild form of depression, in Italy. Amisulpride has also been demonstrated to be an antidepressant for patients with major depression in many clinical trials. In part because of the selective D₂/D₃ receptor antagonist properties of amisulpride, it has long been widely assumed that dopaminergic modulation is the proximal event responsible for mediating its antidepressant and antipsychotic properties.

The purpose of these studies was to determine if amisulpride’s antidepressant actions are mediated by off-target interactions with other receptors.

We performed experiments that: (1) examined the pharmacological profile of amisulpride at a large …