MCH Receptor 1 Antagonists: Antidepressant/Anxiolytic Potential in Animal Models

  • Shigeyuki ChakiEmail author


Melanin-concentrating hormone (MCH), a cyclic 19-amino acid neuropeptide, has been involved in a variety of physiological events, including the regulation of stress responses and mood. Two subtypes of MCH receptor, MCH1 and MCH2, have been identified, and MCH1 mediates most of the physiological functions of MCH.

To date, numerous non-peptidic MCH1 antagonists have been developed, and studies using these MCH1 antagonists and genetically manipulated mice lacking MCH1 have revealed that the blockade of MCH1 produces antidepressant and anxiolytic effects in a variety of rodent models. In addition, the mechanisms underlying the antidepressant/anxiolytic effects of MCH1 antagonists have been investigated, and the regulation of the hypothalamus-pituitary-adrenal axis activity, mesolimbic dopaminergic system, and serotonergic system may be responsible for the stress-coping and mood-modulating effects of MCH1 antagonists. Importantly, MCH1 antagonists showed a faster onset of action, compared with currently available medications, and a smaller number of side effects, compared with conventional antidepressants and anxiolytic treatments. Therefore, MCH1 antagonists may enable improved treatment for depression and anxiety disorders and deserve further investigation, particularly in clinical trials, as potential new treatments for these disorders.


Melanin-concentrating hormone 1 receptor Antidepressant Anxiolytic Animal model Serotonin Dopamine 


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Research Headquarters, Taisho Pharmaceutical Co., Ltd.SaitamaJapan

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