Analyses of FR127519 and KSG-504 as cholecystokininA receptor antagonists in the rat isolated nodose ganglion

Philip M. Beart, Elena Krstew, Robert E. Widdop

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Two structurally novel CCKA receptor antagonists, FR127519 and KSG-504, were examined in the rat nodose ganglion, a convenient model system allowing the functional characterization of CCKA-mediated responses of vagal sensory neurones. Both CCKA antagonists attenuated the actions of CCK in a concentration-dependent manner. FR127519, 3 and 10nM, produced rightward shifts in the CCK dose-response curve of 3.2- and 5.2-fold, from which apparent -log KB values of 8.86 and 8.63, respectively, were calculated. Similar experiments were performed with 30 and 300 nM KSG-504, and although the lower concentration shifted the CCK dose-response curve in a non-parallel manner, the data obtained with 300 nM (6.6-fold parallel shift) allow the determination of an apparent -log KB value of 7.27. From these and previous data a rank order of potency of CCKA antagonists was determined: devazepide> SR 27897B> FR127519> PD140548> KSG-504. FR127519 and KSG-504 were efficacious CCKA receptor antagonists which may be clinically useful in pancreatitis, and the management of gastrointestinal and lung carcinomas.

Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalPharmacology Reviews and Communications
Volume9
Issue number1-2
Publication statusPublished - 1 Dec 1997

Keywords

  • Cholecystokinin
  • Nodose ganglion
  • Rank potency
  • Receptor antagonists

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