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A cholecystokinin receptor antagonist is a specific type of receptor antagonist which blocks the receptor sites for the peptide hormone cholecystokinin.
There are two subtypes of this receptor known at present, defined as CCKA and CCKB. The CCKA receptor is mainly expressed in the small intestine, and is involved in the regulation of enzyme secretion by the pancreas, secretion of gastric acid in the stomach, intestinal motility and signaling of satiety. The CCKB receptor is expressed mainly in the central nervous system, and has functions relating to anxiety and the perception of pain. Antagonists for the CCK receptors can thus have multiple functions in both the gut and brain.
The best known CCK receptor antagonist is the non-selective antagonist proglumide, which blocks both CCKA and CCKB receptors, and was originally developed for the treatment of stomach ulcers. This action derived from its blockade of CCKA receptor in the gut and consequent reduction in secretion of gastric acid, however a side effect of proglumide was found, namely that it increases the analgesic effects of opioid painkillers, and decreases the development of tolerance. This was subsequently found to result from its blockade of CCKB receptors in the brain.
Newer drugs have since been developed which are selective for one or other of the CCK receptors. Selective CCKA receptor antagonists such as lorglumide and devazepide have been developed both for their anti-ulcer effects and as potential drugs to limit the development of gastrointestinal cancers such as colon cancer.