MEN10376 is a peptide neurokinin-2 (NK2) receptor antagonist.1 It inhibits contractions induced by neurokinin A (NKA) in endothelium-deprived isolated rabbit pulmonary artery (pA2 = 8.08), which is endogenously enriched in NK2 receptors. It is selective for NK2 receptors in isolated rabbit pulmonary artery over NK2 receptors in isolated hamster trachea (pA2 = 5.64 using NKA as an agonist) and NK1 receptors in isolated guinea pig ileum (pA2 = 5.66 using substance P methyl ester as an agonist), tissues that highly express these respective receptors, as well as NK3 receptors in isolated guinea pig cerebral cortex membranes (Ki = >10 μM). In vivo, MEN10376 (1 and 3 μmol/kg) inhibits increases in bladder motility induced by the NK2 receptor agonist [β-Ala8]-NKA(4-10) in anesthetized rats, as well as [β-Ala8]-NKA(4-10)-induced increases in bronchoconstriction in anesthetized guinea pigs.
1.Maggi, C.A., Giuliani, S., Ballati, L., et al.In vivo evidence for tachykininergic transmission using a new NK-2 receptor-selective antagonist, MEN 10,376J. Pharmacol. Exp. Ther.257(3)1172-1178(1991)