Consensus on the use of substituted benzamides in psychiatric patients

The class of substituted benzamides includes compounds able to modulate dopaminergic neurons selectively and specifically. The first synthetic substituted benzamide was sulpiride, which has been replaced in the clinic by the more modern amisulpride. The compound is very selective for mesolimbic D₂ and D₃ receptors and, therefore, has a dual mechanism of action, which is associated with two different indications. At low doses (50 mg), amisulpride preferentially blocks presynaptic autoreceptors, producing an increase in dopamine release, and therefore acting as a dopaminergic compound able to resolve the dopaminergic hypoactivity that characterizes depression. At higher doses (400-1,200 mg), the drug exerts its activity on postsynaptic D ₃/D₂ receptors located in the limbic region and prefrontal areas, producing selective dopaminergic inhibition, eliciting antipsychotic effects. In the present review, the clinical use of amisulpride in depressive syndromes is discussed, in particular in dysthymia and in schizophrenia. Based on experimental data, amisulpride is a treatment of choice for dopaminergic transmission disorders, both in depression and in schizophrenia.