Corticotropin-releasing hormone (CRH) secreted from the hypothalamus is the major regulator of pituitary corticotropin-release and consequent glucocorticoid secretion. Antalarmin is a selective, nonpeptide antagonist of the CRH receptor 1 (Ki = 1 nM) that, consequently, reduces the release of corticotropin in response to chronic stress. Through its antagonism of central CRH signaling, antalarmin can reduce endocrinological, cardiovascular, and behavioral responses to stressful stimuli. It has also been shown to reduce dose escalation in cocaine-addicted rats, to produce anti-inflammatory effects in arthritis models, and to suppress stress-induced gastric ulceration related to irritable bowel syndrome.
