Nonpeptide corticotropin releasing hormone type 1 receptor antagonists as medications, and imaging agents

Corticotropin-releasing hormone (CRH) is produced in the brain and in the periphery and coordinates the body's response to stress. When CRH is synthesized and released from the hypothalamus, it activates the release of adrenocorticotropic hormone from the pituitary, which stimulates adrenal release of cortisol, the principal adrenal steroid hormone in primates. CRH and CRH-like molecules are produced in the CNS and act as peptide neurotransmitters. The regional actions of CRH in the CNS are varied and only partially understood. In addition to regulation of the hypothalamic-pituitary-adrenal axis, CRH coordinates other hormones as well as autonomic, immune and behavioral responses to stress. Aberrant CRH action is implicated in many diseases including addiction, depression, anxiety and eating disorders. In order to understand the physiological role of CRH and the pharmacological actions of the CRHR1 antagonists, we have developed a radiolabeled CRHR1 ligand as an in vivo imaging agent.