In vivo and in vitro characterization of antalarmin, a nonpeptide corticotropin-releasing hormone (CRH) receptor antagonist: suppression of pituitary ACTH release and peripheral inflammation

Endocrinology. 1996 Dec;137(12):5747-50. doi: 10.1210/endo.137.12.8940412.


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. CRH receptors (CRH-R1, R2alpha, R2beta) exhibit a specific tissue distribution. Antalarmin, a novel pyrrolopyrimidine compound, displaced 12SI-oCRH binding in rat pituitary, frontal cortex and cerebellum, but not heart, consistent with antagonism at the CRHR1 receptor. In vivo antalarmnin (20 mg/kg body wt.) significantly inhibited CRH-stimulated ACTH release and carageenin-induced subcutaneous inflammation in rats. Antalarmin, or its analogs, hold therapeutic promise in disorders with putative CRH hypersecretion, such as melancholic depression and inflammatory disorders.

MeSH terms

  • Adrenocorticotropic Hormone / antagonists & inhibitors*
  • Adrenocorticotropic Hormone / metabolism
  • Animals
  • Binding, Competitive
  • Carrageenan / administration & dosage
  • Carrageenan / pharmacology
  • Cerebellum / metabolism
  • Corticotropin-Releasing Hormone / metabolism
  • Frontal Lobe / metabolism
  • Inflammation / chemically induced
  • Inflammation / prevention & control
  • Injections, Subcutaneous
  • Male
  • Myocardium / metabolism
  • Pituitary Gland / metabolism*
  • Pyrimidines / pharmacology*
  • Pyrroles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Sheep


  • Pyrimidines
  • Pyrroles
  • Receptors, Corticotropin-Releasing Hormone
  • antalarmin
  • Carrageenan
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone