CCK agonists and antagonists

Miller reported several monomeric, photolabile CCK agonists and antagonists. The photoreactive residue (L-Bpa) was placed at the N-terminal and a fluorescent reporter group was also linked to it. The CCK receptor in the study was expressed on Chinese hamster ovary-CCKR cells. To identify the labeled domains on the receptor capillary electrophoresis was used with laser induced fluorescence detection. Separate regions were labeled with the two photoprobes, one labeled the first extracellular loop (96-121), while the other probe labeled a fragment in the second extracellular loop (174-195). 

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. 

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. 

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... 

The panicogenic effects of CCK-B agonists and the ability of CCK-B antagonists to block this effect raise the question of therapeutic efficacy of CCK-B antagonists on spontaneous panic attacks. Thus far, the only clinical trial carried out is inconclusive. Kramer and colleagues [1995] used a multicenter, placebo-controlled, double-blind trial to investigate the efficacy of L-365,260 [30 mg four times a day] in patients with panic disorder with or... 

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. 

Tifluadom is a 2-[(acylamino)methyl]-l,4-benzodiazepine (Fig. 8), with K-agonist and cholecystokinin-A (CCK-A) antagonist abilities [29]. Cappelli and colleagues successfully discriminated KORs from CCKs, and KORs from MORs using the 2-[(acylamino)ethyl] derivatives [29, 31]. Although tifluadom is a racemic... 

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