We summarize the alterations of classical neurotransmitters and neuropeptides and the corresponding subreceptors
involved in major depression. Neuronal circuits in the brainstem, hippocampus and hypothalamus are developed,
since they can be used to derive a multimodal pharmacotherapy. In this sense, serotonin hypoactivity could occur through
a strong presynaptic inhibition of glutaminergic neurons via the subtype 5 of metabotropic glutaminergic receptors, and
noradrenaline hypoactivity could be due to an enhanced presynaptic inhibition of GABAergic neurons via GABAB receptors.
In the hippocampus, dopamine hypoactivity leads to a decreased positive effect. In clinical trials, the antidepressant
effect of drugs interfering with the mentioned subreceptors, for example the triple reuptake inhibitor amitifadine, is being
investigated. Moreover, the alterations of neuropeptides, such as corticotropin-releasing hormone, neuropeptide Y and
galanin are pointed out. The additional antidepressant effect of analogs, agonists and antagonists of the mentioned neuropeptides
should be examined.