CCK-A receptor agonists

Cholecystokinin. Cholecystokinin (CCK) is also colocalized with dopaminergic neurons and has two receptor subtypes, CCK-A being predominantly outside of and CCK-B within the central nervous system. Studies of CCK agonists and antagonists to date have not given clear clues as to their potential for therapeutic actions in schizophrenia. 

Cholecytokinin ligands - agonists of the central CCK receptors cause anxiety and precipitate panic attacks in predisposed individuals. Two types of CCK receptors have been identified, CCK-A and -B (from the alimentary tract and brain respectively), both of which occur in the mammalian brain. CCK-B agonists initiate anxiety while the antagonists are anxiolytic in both experimental and clinical situations. So far the poor bioavailability and side effects have limited their clinical development. 

CCKa receptors show an order of potency as follows CCK-8 gastrin = desulphated-CCK-8 > CCK-4. The peptide analogue A 71623 is regarded as a selective agonist. 

Cholecystokinin (CCK) is one of a number of peptides that act both as gut hormones and neurotransmitters in the central nervous system (CNS). Through the discovery of selective agonists and antagonists it has been possible to show that CCK acts through at least two receptor subtypes, CCK-A and CCK-B. The former are found mainly in the periphery, whilst the latter are located extensively in the CNS. 

If cADPR is a mediator of pharmacomechanical coupling in some smooth muscle cells, then agonists should modulate its intracellular levels. This has not been demonstrated yet, however, two cell-surface receptor agonists that would be good candidates are cholecystokinin (CCK) in rabbit longitudinal muscle... 

In view of the most recent results which indicate distinct binding sites for agonists and antagonists on CCK-A and CCK-B receptors (156-158,166), this lack... 

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