CCK-B receptor antagonists

Finally, the peptide can induce anxiety and panic in normal and anxious volunteers. Some synthetic CCK-B receptor antagonists are chemically similar to the benzodiazepine anxiolytics. Again, the clinical role of CCK manipulation in anxiety remains to be resolved. 

Bradwejn J, Koszycki D, Payeur R Study of the replication of action of cholecystokinin in panic disorders. Am J Psychiatry 149 962-964, 1992c Bradwejn J, Koszycki D, Couetoux-Dutertre AC, et al L-365,260, a CCK-B receptor antagonist, blocks CCK-4 panic (oral presentation). Presented at the annual meeting of the Anxiety Disorders Association of America (NR 235), Charleston, SC, March 20, 1993... 

Yuki H, Nishida A, Miyake A et al. (1997) YM022, a potent and selec-tive gastrin/CCK-B receptor antagonist, inhibits peptone meal-induced gastric secretion in Heidenhain pouch dogs. Dig Dis Sci 42 707-714... 

Drysdale, M. J., Pritchard, M. C., Horwell, D. C. Rationally designed dipeptoid analogues of CCK. Acid mimics of the potent and selective non peptide CCK-B receptor antagonist Cl-988. J. Med. Chem. 1992,35,2573-2581. 

Amongst the compounds synthesised, GV150013 was found to be a highly potent (pKg = 9.2) and selective CCK-B receptor antagonist. It showed potent anxiolytic activity in a number of animal models and it has been progressed into development. 

The classification of CCK receptors into two sub-types is supported by the use of non-peptidic, selective competitive antagonists. L-364,718 (devazepide) was the first competitive antagonist found with high affinity for the CCK-A receptor (pKj = 9.3) [9]. This compound was developed from asperlicin (pKj = 6.2) which had been found during the screening of products of microbiological fermentation [10]. Similarly, a number of selective CCK-B receptor antagonists have been discovered such as the peptoid PD-134308 (pK = 8.5) which was derived from a chemical manipulation of CCK-4 [11]. 

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