Corticotropin-releasing factor antagonists in affective disorders
- 1 November 1999
- journal article
- Published by Taylor & Francis in Expert Opinion on Investigational Drugs
- Vol. 8 (11) , 1849-1858
- https://doi.org/10.1517/13543784.8.11.1849
Abstract
Following a search lasting nearly three decades, corticotropin-releasing factor (CRF), a 41 amino acid-containing peptide, was isolated and characterised in 1981. In the preceding 18 years, a concatenation was developed that appears to show that CRF integrates not only the endocrine, but also the autonomic, immunologic and behavioural responses of mammalian organisms to stress. Direct CNS administration of CRF to laboratory animals produces actions similar to those observed after exposure to stress. Moreover, CNS administration of peptidergic CRF antagonists blocks many of the behavioural responses to stress. Since both early untoward life events as well as recently experienced stress have been implicated in the pathophysiology of affective disorders, and because there is substantial evidence for CRF neuronal hyperactivity in patients with affective disorders, small molecule, lipophilic CRF antagonists have been hypothesised to possess antidepressant and/or anxiolytic activity. Within the last few years, ...Keywords
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