Evaluation of a series of novel CCKB antagonists using a functional assay in the rat central nervous system

• Published in: British journal of pharmacology 1994-06, Vol.112 (2), p.666-670
• Main Authors: Boden, P.R., Pinnock, R.D., Pritchard, M.C., Woodruff, G.N.
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Animals; Biological and medical sciences; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; electrophysiology; hypothalamus; In Vitro Techniques; Ligands; Male; Medical sciences; Mice; Miscellaneous; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Novel CCKB antagonists; Pentagastrin - antagonists & inhibitors; Pharmacology. Drug treatments; Rats; Rats, Wistar; Receptors, Cholecystokinin - antagonists & inhibitors; Structure-Activity Relationship; Ventromedial Hypothalamic Nucleus - drug effects; Ventromedial Hypothalamic Nucleus - metabolism
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1994.tb13127.x

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 evaluated for their ability to reduce pentagastrin‐induced increases in action potential firing rate. 3 All twenty compounds studied were found to be CCKB antagonists, with equilibrium constants spanning a concentration‐range of several orders of magnitude. The rank order for their ability to block pentagastrin responses correlated well with values obtained for their relative affinities for the mouse cortex CCKB binding site. 4 It is concluded that the VMH preparation provides a good functional correlate to binding assays in the rodent central nervous system for a structurally diverse series of CCKB antagonists.