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.
E L Webster  1 ,  D B Lewis ,  D J Torpy ,  E K Zachman ,  K C Rice ,  G P Chrousos
Affiliations
  • 1. Pediatric Endocrinology Section, DEB, NICHD, National Institutes of Health, Bethesda, MD 20892, USA.
PMID: 8940412 DOI: 10.1210/endo.137.12.8940412
Abstract

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.

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