Development of CRF1 Receptor Antagonists as Antidepressants and Anxiolytics (original) (raw)

that are considered to be stress-related disorders because some form of stressful life event often triggers their symptoms. Corticotropin-releasing factor (CRF) is a 41-amino-acid neuropeptide involved in mediating neuroendocrine, autonomic and behavioural responses to stress, and clinical studies provide evidence for the role of CRF in the development of depression and anxiety disorders. Two CRF receptor subtypes have been identified to date-the CRF1 receptor and the CRF2 receptor. Preclinical models provide evidence of a role for CRF1 receptors in the activation of the stress response. Data from these experiments suggest that antagonism of CRF1 receptor activity may provide an effective pharmacological treatment for stress-related psychiatric disorders. This review highlights progress to date with the development of CRF1 receptor antagonists as potential pharmacotherapies for depression and anxiety disorders. Although additional research is needed to fully investigate the efficacy and safety profiles of CRF1 receptor antagonists as candidate medications for these disorders, the results of preclinical experiments and clinical trials are encouraging. Further development of these compounds is warranted. Depression and anxiety disorders are highly Corticotropin-releasing factor (CRF) is a 41amino-acid neuropeptide involved in mediating prevalent forms of mental illness. Worldwide, deneuroendocrine, [5] autonomic [6,7] and behavioural repression will have a lifetime occurrence of 8-12% in sponses to stress. [8,9] CRF is the main regulator of all individuals. [1] In addition, in the US alone apthe hypothalamic-pituitary adrenal (HPA) axis proximately 30% of all adults will experience some stress response, which has been traditionally used by form of anxiety disorder at some point during their biologists as a method of quantifying stress. [5] lives. [2] These conditions place a considerable economic burden on society [1,3] and have a high preva-Results from clinical studies suggest a role for lence of comorbidity. [4] Often, stressful life events CRF in the development of depression and anxiety trigger or worsen the symptoms of these disorders, disorders. For example, CRF levels are elevated in and patients diagnosed with them have difficulty the CSF of patients diagnosed with post-traumatic coping with stress. stress disorder. [10] Clinically depressed individuals