A Second Generation of Non-Peptide Cholecystokinin Receptor Antagonists and Their Possible Therapeutic Potential
| Autor: | Stephen B. Freedman, Kerry L. Chapman, Kate Scholey, George R. Marshall, Mark G. Bock, Roger M. Freidinger, Richard Hargreaves, Robert M. DiPardo, Alan E. Fletcher, John A. Kemp, S. Patel, E. C. Mellin, Alison J. Smith |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Microdialysis
Molecular Structure Chemistry General Neuroscience Ligand binding assay digestive oral and skin physiology Antagonist Pharmacology digestive system Cholecystokinin receptor General Biochemistry Genetics and Molecular Biology Benzodiazepines Structure-Activity Relationship History and Philosophy of Science In vivo Drug Design Animals Pyrazoles Gastric acid Receptors Cholecystokinin Receptor hormones hormone substitutes and hormone antagonists Ex vivo |
| Zdroj: | Annals of the New York Academy of Sciences. 713:312-318 |
| ISSN: | 1749-6632 0077-8923 |
| Popis: | The profile of an acidic series of benzodiazepine CCK-B receptor antagonists is described. The tetrazolyl urea derivative L-368,935 had high affinity (CCK-B IC50 0.1 nM) and was one of the most selective (CCK-B/CCK-A 10,000) CCK-B antagonists known. L-368,935 was a CCK-B antagonist with high affinity on the rat ventromedial hypothalamic slice preparation (Kb 0.6 nM) and also blocked pentagastrin-induced calcium mobilization in GH3 cells. L-368,935 had potent in vivo activity and antagonized pentagastrin-induced gastric acid secretion in the anesthetized rat and CCK-8S-induced aspartate release using microdialysis in the striatum of conscious rats. Activity within the central nervous system was confirmed by a mouse ex vivo binding assay and by direct measurement of the compound within the central nervous system using an HPLC assay. A second generation of CCK-B receptor antagonists such as L-368,935 will be important in determining the therapeutic potential of this class of compound in man. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text