The dipeptide neurokinin-1 receptor antagonist S19752 is a potent and long-acting inhibitor of bronchoconstriction when administered by aerosol to the guinea pig in vivo

The K+ salt of Tbi-Hyp-Trp-OTfb (S19572, Tbi = 1-[4-(2H-tetrazol-5-yl)-butyl]-1H-indole-3-carbonyl; Tfb = 3,5-di-trifluoromethyl-benzyl) is a chemically modified, water-soluble derivative designed from prolyl-tryptophan using N- and C-terminal substitutions to confer on the analogs receptor selectivity and water solubility. The new NK-1 selective receptor antagonist is both highly potent in binding and bioassays in vitro, and long-acting when administered by aerosol to the guinea-pig in vivo. Molecular modeling of the antagonist in the seven transmembrane NK-1 receptor model offers a rationale for the observed water solubility and yet retained binding affinity.