A Potent Nonpeptide Antagonist of the Substance P (NK 1 ) Receptor

作者：R. Michael Snider, Jay W. Constantine, John A. Lowe III, Kelly P. Longo, Wesley S. Lebel, Heidi A. Woody, Susan E. Drozda, Manoj C. Desai, Fredric J. Vinick, Robin W. Spencer, Hans-Jürgen Hess · 发表于：Science · 年份：1991 · DOI：10.1126/science.1703323 · 被引用次数：865 · 研究领域：Neuropeptides and Animal Physiology、Receptor Mechanisms and Signaling、Coagulation, Bradykinin, Polyphosphates, and Angioedema

CP-96,345 [(2S, 3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)- methyl]-1-azabicyclo[2.2.2]octan-3-amine] is a potent nonpeptide antagonist of the substance P (NK1) receptor. CP-96,345 inhibited 3H-labeled substance P binding and was a classical competitive antagonist in the NK1 monoreceptor dog carotid artery preparation. CP-96,345 inhibited substance P-induced salivation in the rat, a classical in vivo bioassay, but did not inhibit NK2, NK3, or numerous other receptors; it is thus a selective NK1 antagonist. This compound may prove to be a powerful tool for investigation of the physiological properties of substance P and exploration of its role in diseases.