Melanocortin Type 2 Receptor Antagonists as a New Treatment Modality in Canine Hypercortisolism in vitro Investigation

Introduction: Hypercortisolism or Cushing’s syndrome is one of the most common endocrinopathies in dogs. Current medical management options consist of the adrenocorticolytic drug mitotane (o,p`-DDD) or the adrenocorticostatic drug trilostane. Both options are effective, yet both may have side-effects. In pituitary-dependent hypercortisolism (PDH), excess cortisol production is caused by hypersecretion of ACTH, which binds to its receptor, the melanocortin type 2 receptor (MC2R), in the adrenal cortex. Blockage of MC2R could therefore be an interesting treatment target to selectively inhibit cortisol production in PDH.

Aim of the study: To assess the effect of two different MC2R antagonists, BIM-776 (776) and BIM-299 (299), on cortisol production in canine primary adrenocortical cell culture. […]