Evaluation of a series of novel CCKB antagonists using a functional assay 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 evaluated for their ability to reduce pentagastrin-induced increases in action potential firing rate. 3. All twenty compounds studies 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.
Boden
P R
PR
Parke-Davis Neuroscience Research Centre, Addenbrookes Hospital Site, Cambridge.
Pinnock
R D
RD
Pritchard
M C
MC
Woodruff
G N
GN
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D051379:Mice; D010418:Pentagastrin / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*
D008024:Ligands; D011949:Receptors, Cholecystokinin; D010418:Pentagastrin