THE DIPEPTIDE NEUROKININ-1 RECEPTOR ANTAGONIST S19752 IS A POTENT ANDLONG-ACTING INHIBITOR OF BRONCHOCONSTRICTION WHEN ADMINISTERED BY AEROSOL TO THE GUINEA-PIG

The K+ salt of Tbi-Hyp-Trp-OTfb (S19572, Tbi = [4-(2H-tetrazol-5-yl)-b utyl]-1H-indole-3-carbonyl; Tfb = 3,5-di-trifluoromethyI-benzyl) is a chemically modified, water-soluble derivative designed from prolyl-try ptophan using N- and C-terminal substitutions to confer on the analogs receptor selectivity and water solubility. The new NK-1 selective rec eptor antagonist is both highly potent in binding and bioassays in vit ro, 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 solubili ty and yet retained binding affinity. (C) 1997, Elsevier Science Ltd.