Chronic administration of the non-peptide CRH type 1 receptor antagonist antalarmin does not blunt hypothalamic-pituitary-adrenal axis responses to acute immobilization stress

Antalarmin is a pyrrolopyrimidine compound that antagonizes corticotropin-r eleasing hormone (CRH) type 1 receptors (CRHR1). In order to assess the eff ects of antalarmin treatment on hypothalamic-pituitary-adrenal (HPA) functi on we measured the plasma concentrations of adrenocorticotropic hormone (AC TH) and corticosterone in animals treated with either antalarmin or vehicle for 1 week or for 8 weeks. We found that antalarmin treatment for 1 week d id not affect basal concentrations of ACTH or corticosterone. In contrast, treatment for 8 weeks significantly lowered basal ACTH and corticosterone c oncentrations and also significantly decreased the basal corticosterone to ACTH ratio, indicating decreased basal adrenocortical responsiveness to ACT H. However, immobilization stress resulted in ACTH and corticosterone conce ntrations that were the same in animals treated with vehicle or antalarmin for either 1 or 8 weeks. We conclude that even though g-week antagonism of CRHR1 by the non-peptide antalarmin blunts basal concentrations of ACTH and corticosterone, and affects the adrenal responsiveness to ACTH, it does no t blunt the HPA response to acute stress, and it does not appear to cause s tress-induced adrenal insufficiency. Published by Elsevier Science Inc.