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Science 25 January 1991:
Vol. 251. no. 4992, pp. 435 - 437
DOI: 10.1126/science.1703323
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Articles

Science, Vol 251, Issue 4992, 435-437
Copyright © 1991 by American Association for the Advancement of Science

articles

A potent nonpeptide antagonist of the substance P (NK1) receptor

RM Snider, JW Constantine, JA Lowe 3rd, KP Longo, WS Lebel, HA Woody, SE Drozda, MC Desai, FJ Vinick, RW Spencer, and al. et

Department of Exploratory Medicinal Chemistry, Central Research Division, Pfizer Inc., Groton, CT 06340.

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.


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Science 251, 437-439
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