In Vivo and In Vitro Characterization of Antalarmin, a Nonpeptide Corticotropin-Releasing Hormone (CRH) Receptor Antagonist: Suppression of Pituitary ACTH Release and Peripheral Inflammation 1.0.0

Antalarmin potently displaced 1251-oCRH binding, exhibiting respectively Ki values of 1. 9 f 0.9,. 1.3 f .4, and 1.4 f .6 nM (mean f SEM) in pituitary, cerebellum, and frontal cortex homogenates.Antalarmin, by effectively displacing IoCRH binding in tissues predominately expressing CRHRl but not in tissues expressing CRHR2, appears to be a specific CRHRl receptor antagonist. PubMed:8940412

Antalarmin potently displaced 1251-oCRH binding, exhibiting respectively Ki values of 1. 9 f 0.9,. 1.3 f .4, and 1.4 f .6 nM (mean f SEM) in pituitary, cerebellum, and frontal cortex homogenates.Antalarmin, by effectively displacing IoCRH binding in tissues predominately expressing CRHRl but not in tissues expressing CRHR2, appears to be a specific CRHRl receptor antagonist. PubMed:8940412

These results raise the possibility that pyrrolopyrimidine compounds, such as antalarmin, which antagonize CRH at the level of its own receptor, have therapeutic potential in some forms of inflammation. PubMed:8940412

Indeed, the compound significantly suppressed (XI-l-induced ACTH secretion to approximately the same extent as neutralizing polyclonal anti-CRH. PubMed:8940412

Corticotropin-releasing hormone (CRH) secreted from the hypothalamus is the major regulator of pituitary ACTH release and consequent glucocorticoid secretion. CRH secreted in the periphery also acts as a proinflammatory modulator. PubMed:8940412