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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

CCK receptor antagonists.

1. The peptide hormone and neurotransmitter, cholecystokinin, is widely distributed throughout the gastrointestinal tract and central nervous system and mediates a diverse number of biological functions. 2. Two receptor subtypes, CCK-A and CCK-B, have been identified by both pharmacological characterization and molecular cloning. The CCK-A receptor is the predominant peripheral CCK receptor subtype and the CCK-B receptor is the predominant central CCK receptor. In addition, there are discrete populations of CCK-A receptors in the brain and CCK-B receptors are present in gastric mucosa. 3. Subtype selective antagonists have been developed which discriminate between the two receptor subtypes. One of the major chemical classes has exploited a benzodiazepine template present in asperlicin which was initially discovered in a natural product screen for CCK receptor antagonists. 4. The structurally related benzodiazepines L-365,260, L-740,093, and YM022 are selective antagonists of the CCK-B receptor subtype. Their in vitro pharmacological profiles have been characterized using the human CCK-B receptor expressed in CHO cells. 5. L-365,260 behaves in a manner consistent with that of a competitive antagonist and both L-740,093 and YM022 behave as insurmountable CCK-B receptor antagonists in vitro.[1]


  1. CCK receptor antagonists. Dunlop, J. Gen. Pharmacol. (1998) [Pubmed]
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