Corticotropin-releasing factor type-1 receptor antagonists: the next class of antidepressants?
Corticotropin-releasing factor (CRF) is a neuropeptide that plays a primary role in the neuroendocrine, autonomic, and behavioral responses to stressors. Numerous reports suggest that alterations in CRF function contribute to the pathogenesis of depression. Recently, selective nonpeptide CRF type 1 (CRF1) receptor antagonists have been discovered and several of these CRF1 receptor antagonists have demonstrated antidepressant-like efficacy in animals. The CRF1 receptor antagonists appear to be unique, as they exhibit antidepressant-like activity principally in animal models that are hyperresponsive to stress or under experimental conditions that alter endogenous stress-hormone activity. A nonpeptide CRF1 receptor antagonist has also been shown to reduce symptoms of major depression in an open-label clinical trial. Accumulating evidence supports a role for nonpeptide CRF1 receptor antagonists among the future pharmacotherapies for the treatment of depression.
Nielsen
Darci M
DM
Center for Alcohol and Addiction Studies, Brown University, Box G-BH, Providence, RI 02912 USA. Darci_Nielsen@Brown.edu
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D003866:Depressive Disorder / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D006380:Helplessness, Learned; D006801:Humans; D051379:Mice; D009830:Olfactory Bulb / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology; D013550:Swimming / Q000523:psychology; D000099052:CRF Receptor, Type 1
D000928:Antidepressive Agents; D011743:Pyrimidines; C412383:R 121919; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone