Abstract
The health burden of stress-related diseases, including depression and anxiety disorders, is rapidly increasing, whereas the range of available pharmacotherapies to treat these disorders is limited and suboptimal with regard to efficacy and tolerability. Recent findings support a major role for neuropeptides in mediating the response to stress and thereby identify neuropeptide systems as potential novel therapeutic targets for the treatment of depression and anxiety disorders. In preclinical models, pharmacological and/or genetic manipulation of substance P, corticotropin-releasing factor (CRF), vasopressin, neuropeptide Y and galanin function alters anxiety- and depression-related responses. Recently, specific and highly potent small-molecule neuropeptide receptor agonists and antagonists have been developed that can readily cross the blood-brain barrier. Clinical assessment of several compounds is currently underway, with antidepressant efficacy confirmed in double-blind, placebo-controlled trials of tachykinin NK(1) (substance P) receptor antagonists, and preliminary evidence of antidepressant activity in an open-label trial of a CRF(1) receptor antagonist.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Animals
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Antidiuretic Hormone Receptor Antagonists
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Anxiety Disorders / drug therapy*
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Anxiety Disorders / metabolism
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Clinical Trials as Topic
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Depressive Disorder / drug therapy*
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Depressive Disorder / metabolism
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Humans
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Neurokinin-1 Receptor Antagonists
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Receptors, Corticotropin-Releasing Hormone / agonists
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Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
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Receptors, Corticotropin-Releasing Hormone / metabolism
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Receptors, Galanin / agonists
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Receptors, Galanin / antagonists & inhibitors
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Receptors, Galanin / metabolism
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Receptors, Neurokinin-1 / agonists
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Receptors, Neurokinin-1 / metabolism
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Receptors, Neuropeptide / agonists*
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Receptors, Neuropeptide / antagonists & inhibitors*
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Receptors, Neuropeptide / metabolism
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Receptors, Neuropeptide Y / agonists
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Receptors, Neuropeptide Y / antagonists & inhibitors
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Receptors, Neuropeptide Y / metabolism
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Receptors, Vasopressin / agonists
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Receptors, Vasopressin / metabolism
Substances
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Antidiuretic Hormone Receptor Antagonists
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Neurokinin-1 Receptor Antagonists
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Receptors, Corticotropin-Releasing Hormone
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Receptors, Galanin
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Receptors, Neurokinin-1
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Receptors, Neuropeptide
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Receptors, Neuropeptide Y
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Receptors, Vasopressin