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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Classical Neurotransmitters and Neuropeptides Involved in Major Depression in a Multi-neurotransmitter System: A Focus on Antidepressant Drugs

Author(s): Felix-Martin Werner and R. Coveñas

Volume 20 , Issue 38 , 2013

Page: [4853 - 4858] Pages: 6

DOI: 10.2174/09298673113206660280

Price: $65

Abstract

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.

Keywords: Corticotropin-releasing hormone, dopamine, GABA, glutamate, neuropeptide Y, noradrenaline, serotonin, substance P.


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