Central Nervous System Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

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The Role of Vasopressin in Affective Disorders: Possible Targets of Intervention

Author(s): Dora Zelena.

Abstract:

The therapy of mood and anxiety disorders are not solved, yet, because current antidepressants have delayed onset of therapeutic action and a significant number of patients are non-responsive. Research on the field was leaning towards neuropeptides as therapeutic targets. The neurohypohyseal hormone vasopressin (VP) is a hot candidate, as beyond its peripheral actions VP is also implicated in interneuronal communication in the central nervous system and modulates behavioral functions such as feeding, learning, memory formation etc. Affective disorders are stress related disorders and for a long time, clinicians suspected a causal link between depression and the endocrine system. The most frequently occurring endocrine abnormality in depressed subjects is hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis. VP with nucleus paraventricularis hypothalami (PVN) origin is a direct adrenocorticotropin secretagogue through its V1b receptors. VP seems to have special importance under prolonged stress conditions, which are known to be strong predictive factor of depressive disorder and can induce depressive-like symptoms in animals. Moreover VP serves as neuromodulator in/between key limbic regions – amygdale, hippocampus, bed nucleus of stria terminalis and PVN. Recently an orally active V1b antagonist was also developed and seemed to have effective anxiolytic profile and its antidepressant-like effect was also demonstrated. Moreover the studies with the high anxiety Wistar rats (HAB) indicate that over-expression and - release of VP in the PVN is responsible for their depressive-like behavioral and neuroendocrine phenomena. Taken together current knowledge strongly implies an importance of vasopressinergic regulation in affective disorders and consider VP as endogenous anxiogenic/antidepressive substance.

Keywords: Vasopressin, anxiety, depression, V1b antagonist, brattleboro rats

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Article Details

VOLUME: 8
ISSUE: 4
Year: 2008
Page: [275 - 285]
Pages: 11
DOI: 10.2174/187152408786848085
Price: $58