CCK-A antagonists

Herbert and McNeil have shown that the appropriate 2-iodoindole can be carbonylated in the presence of primary and secondary amines to afford the corresponding 2-indolecarboxamides in 33-97% yield. Further application of this protocol leads to amide 319, which is a CCK-A antagonist (Lintitript) [420]. 

Cl-988 has been found to reduce the behavioral stress in marmosets exposed to a human threat [Hughes et al. 1990]. L-365,260 can antagonize the behavioral effects of exposition to the odor of a cat in rats and suppress the behavioral reaction of mice to the calls of an owl, an effect also found with LY 288513 (Hendrie and Dourish 1994]. Thus, evidence suggests an anxiolytic activity of CCK-B antagonists. The activity seems more evident in etho-logically based models of anxiety than in conflict-based tests and does not follow a linear dose-dependent relationship but rather a bell-curve one. Also, most studies point to a selectivity of CCK-B antagonists, but not CCK-A antagonists, for anxiolytic effects. 

Intravenous infusion of an octapeptide derivative of CCK decreases the level of hunger and reduces food intake in normal subjects (Kissileff et al. 1981). This effect is reversed by loxiglumide, a specific CCK-A antagonist (Gutzwiller et al. 2000). 

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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