EVALUATION OF A SERIES OF NOVEL CCK(B) ANTAGONISTS USING A FUNCTIONALASSAY IN THE RAT CENTRAL-NERVOUS-SYSTEM

1 Electrophysiological recordings from rat ventromedial hypothalamus ( VMH) in vitro have been used to compare the effects of novel chemical entities on CCKB receptor activation in the rat central nervous system . 2 Twenty compounds from three different chemical series were evaluat ed for their ability to reduce pentagastrin-induced increases in actio n potential firing rate. 3 All twenty compounds studied were found to be CCKB antagonists, with equilibrium constants spanning a concentrati on-range of several orders of magnitude. The rank order for their abil ity to block pentagastrin responses correlated well with values obtain ed for their relative affinities for the mouse cortex CCKB binding sit e. 4 It is concluded that the VMH preparation provides a good function al correlate to binding assays in the rodent central nervous system fo r a structurally diverse series of CCKB antagonists.