CHOLECYSTOKININ ANALOGS WITH SUPPRESSED CENTRAL ACTIVITIES

Several analogs of Boc-protected C-terminal heptapeptide of cholecysto kinin (Boc-CCK-7) with modified C-end Phe were pharmacologically chara cterized. The influence of the number of methyl groups on aromatic sid e chain of Phe was investigated in following tests: binding to pancrea tic and brain membrane receptors, gall bladder contraction, amylase se cretion, anorexia, sedation and analgesia. Two analogs seem to be prom ising selective anorectic agents with strongly protracted effect: Boc- [Phe(triMe)(7)]CCK-7 and Boc-[Phe(pentaMe)(7)]CCK-7. The first analog exhibits the same spectrum of activities as CCK-S, however partially d ecreased central effects, the second one shows partially decreased per ipheral activities and totally suppressed central ones. Our study supp orts the idea that C-terminal residue of CCK is more important for bio logical potency than for binding to CCK receptors. (C) 1998 Elsevier S cience Inc.