Therapeutic potential of CRF receptor antagonists: a gut-brain perspective

Activation of the corticotropin-releasing factor (CRF) family of neuropepti de receptors in the brain and periphery appears to mediate stress-related c hanges in a variety of physiological and functional domains. Comparative ph armacology of CRF receptor agonists suggests that CRF, urocortin, sauvagine and urotensin consistently mimic, and conversely peptide CRF receptor anta gonists lessen, the functional consequences of stressor exposure. Together with the development of novel non-peptide CRF receptor antagonists, a growi ng number of CRF receptor selective ligands are available to elucidate the neurobiology and physiological role of CRF systems. The present review cons iders available preclinical evidence as well as results from one Phase II c linical trial which address the hypothesis that CRF receptor antagonists ma y represent a new option for pharmacotherapy of stress-related disorders.