Ibodutant -: Tachykinin NK2 receptor antagonist treatment of irritable bowel syndrome

Tachykinins are widely expressed endogenous peptides in mammals endowed with physiological and pathophysiological effects. The potent effects of tachykinins on smooth muscle, local inflammatory effects and visceral hypersensitivity observed in human intestine are mainly mediated by NK2 receptors. Ibodutant (MEN-15596) is a potent and selective tachykinin NK2 receptor antagonist with a simple chemical structure and one chiral center. It competitively and selectively antagonizes the NK2 receptor with subnanomolar affinity, both in animal and human tissues, and blocks NK2 receptor-mediated effects, with a good oral bioavailability and long duration of action. Ibodutant inhibited visceral hyperalgesia evoked by colorectal distension in inflamed unanesthetized guinea pigs, whereas it was without effect on rectal distension-induced abdominal contractions in control animals. Ibodutant showed a very good safety profile in a series of studies, including in vivo cardiovascular safety evaluation using telemetry in dogs. It has successfully completed phase I clinical studies and is currently in phase II clinical development for the oral treatment of irritable bowel syndrome (IBS).