Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders.
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.
Holmes
Andrew
A
Section on Behavioral Science and Genetics, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. ahlomes@intra.nimh.nih.gov
Heilig
Markus
M
Rupniak
Nadia M J
NM
Steckler
Thomas
T
Griebel
Guy
G
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D064729:Neurokinin-1 Receptor Antagonists; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D044088:Receptors, Galanin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000819:agonists / Q000378:metabolism
D065092:Antidiuretic Hormone Receptor Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D018019:Receptors, Corticotropin-Releasing Hormone; D044088:Receptors, Galanin; D018040:Receptors, Neurokinin-1; D018013:Receptors, Neuropeptide; D017476:Receptors, Neuropeptide Y; D017483:Receptors, Vasopressin