Osanetant (hydrate) (Synonyms: SR 142801)

Osanetant is a neurokinin-3 (NK₃) receptor antagonist (K_i = 0.21 nM in CHO cells expressing the human receptor).¹ It is selective for NK₃ over NK₁ and NK₂ receptors (K_is = >100 and 0.02 µM, respectively).² Osanetant inhibits contractions and acetylcholine release induced by neurokinin B in isolated guinea pig ileal strips in a concentration-dependent manner.¹ It inhibits ovalbumin-induced increases in bronchoalveolar lavage fluid (BALF) neutrophil, eosinophil, and lymphocyte infiltration in an ovalbumin-sensitized mouse model of allergic asthma.³ Osanetant (5 and 10 mg/kg) increases the duration of social interaction, as well as reduces immobility time in the tonic immobility test, indicating anxiolytic-like and antidepressant-like activities, respectively, in gerbils.⁴

1.Emonds-Alt, X., Bichon, D., Ducoux, J.P., et al.SR 142801, the first potent non-peptide antagonist of the tachykinin NK3 receptorLife Sci.56(1)PL27-PL32(1995) 2.Griebel, G., and BeeskÉ, S.Is there still a future for neurokinin 3 receptor antagonists as potential drugs for the treatment of psychiatric diseases•Pharmacol. Ther.133(1)116-123(2012) 3.NÉnan, S., Germain, N., Lagente, V., et al.Inhibition of inflammatory cell recruitment by the tachykinin NK3-receptor antagonist, SR 142801, in a murine model of asthmaEur. J. Pharmacol.421(3)201-205(2001) 4.SalomÉ, N., Stemmelin, J., Cohen, C., et al.Selective blockade of NK2 or NK3 receptors produces anxiolytic- and antidepressant-like effects in gerbilsPharmacol. Biochem. Behav.83(4)533-539(2006)