CORTICOTROPHIN-RELEASING FACTOR RECEPTOR ANTAGONISTS

CORTICOTROPHIN-RELEASING FACTOR RECEPTOR ANTAGONISTS inhibit the actions of agents related to corticotrophin-releasing factor (CRF). Two subtypes of receptor, CRF, and CRF2, have recently been identified and cloned, and there is interest in these as therapeutic targets. See CORTICOTROPHIN-RELEASING FACTOR RECEPTOR AGONISTS.

Some peptide antagonists that have some affinity for both CRF, and CRF2 receptors have been developed by making modifications of the CRF sequence, and these include; a-helicalCRE9-41,DPhe-CRF12-41 and the peptide astressm. Recently, some related non-peptides that act selectively at CRF, receptors have been developed including CP 154526, NB 127914 and antalarmin. A number of other agents are currently the subject of patent applications.

Some possibly clinical applications of CRF receptor ligands are discussed in relation to evidence about the role of CFG; see corticotrophin-releasing factor receptor agonists. It might be hypothesized that corticotrophin-releasing factor antagonists could be used clinically to treat panic and generalized anxiety disorders, and possibly also to treat clinical depression and anorexia. Similarly, there is some evidence suggesting that stroke might be treatable with CRF receptor antagonists acting on the cerebral vasculature. Inflammatory disorders offer tempting targets for CRF-related novel drugs. In experimental models, CRF is pro-inflammatory, and a number of animal models of inflammation show increased corticotrophin-releasing factor expression. Further, there is enhanced expression of immunoreactive CRF in the synovium of the joints of patients with rheumatoid arthritis. It remains to be seen whether CRF receptor antagonists might be of value in the treatment of rheumatic conditions. However, it is not yet clear which receptor subtypes are involved in these inflammatory responses or in other components of inflammation, such as pyrexia.