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

Two structurally novel CCK_A receptor antagonists, FR127519 and KSG-504, were examined in the rat nodose ganglion, a convenient model system allowing the functional characterization of CCK_A-mediated responses of vagal sensory neurones. Both CCK_A 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 K_B 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 K_B value of 7.27. From these and previous data a rank order of potency of CCK_A antagonists was determined: devazepide> SR 27897B> FR127519> PD140548> KSG-504. FR127519 and KSG-504 were efficacious CCK_A receptor antagonists which may be clinically useful in pancreatitis, and the management of gastrointestinal and lung carcinomas.