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.
Current Medicinal Chemistry
Title:Classical Neurotransmitters and Neuropeptides Involved in Major Depression in a Multi-neurotransmitter System: A Focus on Antidepressant Drugs
Volume: 20 Issue: 38
Author(s): Felix-Martin Werner and R. Coveñas
Affiliation:
Keywords: Corticotropin-releasing hormone, dopamine, GABA, glutamate, neuropeptide Y, noradrenaline, serotonin, substance P.
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.
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Werner Felix-Martin and Coveñas R., Classical Neurotransmitters and Neuropeptides Involved in Major Depression in a Multi-neurotransmitter System: A Focus on Antidepressant Drugs, Current Medicinal Chemistry 2013; 20 (38) . https://dx.doi.org/10.2174/09298673113206660280
DOI https://dx.doi.org/10.2174/09298673113206660280 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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