Pharmacological profiles of new orally active nonpeptide tachykinin NK1 receptor antagonists

European Journal of Pharmacology
R HosokiM Otsuka

Abstract

Pharmacological profiles of new orally active amide-based tachykinin NK1 receptor antagonists, N-[3,5-bis(trifluoromethyl)benzyl]-5-(4-fluorophenyl)-7,8-dihydro-N,7-di methyl-8-oxo-1,7-naphthyridine-6-carboxamide (referred to as compound I) and two related compounds (compounds II and III), were compared with that of (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994), another nonpeptide tachykinin NK1 receptor antagonist. Compounds I, II, III and CP-99,994 caused parallel rightward shifts of the concentration-response curve of substance P in the guinea-pig ileum pretreated with atropine, mepyramine and indomethacin, with the pA2 values of 8.70, 7.56, 8.41 and 8.27, respectively. These antagonists did not alter the concentration-response curve of acetylcholine in the guinea-pig ileum nor that of neurokinin A in the rat vas deferens. Furthermore, contractile responses to senktide of the rat portal vein were not affected by these antagonists. In the isolated neonatal gerbil spinal cord pretreated with tetrodotoxin, substance P produced a dose-dependent depolarization of ventral roots. Compounds I, II, III and CP-99,994 caused parallel rightward shifts of the concentration-response curve of substance P in the spinal...Continue Reading

References

Nov 1, 1992·British Journal of Pharmacology·T FujiiM Matsuo
Aug 1, 1990·British Journal of Pharmacology·M Yanagisawa, M Otsuka
Jan 25, 1991·Science·R M SniderR W Spencer
May 17, 1991·European Journal of Pharmacology·B D GitterJ J Howbert
Nov 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·C GarretP M Laduron
Nov 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·R LauferZ Selinger
Nov 1, 1987·Pain·D Papir-KricheliM Devor
Feb 24, 1987·European Journal of Pharmacology·D MastrangeloD Regoli
Mar 1, 1982·Naunyn-Schmiedeberg's Archives of Pharmacology·C M LeeB E Sandberg
Apr 1, 1980·Neuroscience Letters·P Holzer, F Lembeck
Jul 2, 1993·Regulatory Peptides·S McLeanJ Heym
Jul 9, 1993·Journal of Medicinal Chemistry·A M MacLeodR Baker
Mar 1, 1959·British Journal of Pharmacology and Chemotherapy·O ARUNLAKSHANA, H O SCHILD

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Citations

Aug 12, 1999·European Journal of Pharmacology·A Saria
Apr 1, 2009·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Saskia P A WolfensbergerAdriaan A Lammertsma
Nov 4, 2000·Expert Opinion on Investigational Drugs·S V Argyropoulos, D J Nutt
Dec 14, 2004·Life Sciences·Luz CandenasJocelyn N Pennefather
Feb 5, 2002·Chemical & Pharmaceutical Bulletin·Atsushi YamamotoMasanori Otsuka

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