title: Cholecystokinin analogs with suppressed central activities.
abstract: Several analogs of Boc-protected C-terminal heptapeptide of cholecystokinin (Boc-CCK-7) with modified C-end Phe were pharmacologically characterized. The influence of the number of methyl groups on aromatic side chain of Phe was investigated in following tests: binding to pancreatic and brain membrane receptors, gall bladder contraction, amylase secretion, anorexia, sedation and analgesia. Two analogs seem to be promising 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-8, however partially decreased central effects, the second one shows partially decreased peripheral activities and totally suppressed central ones. Our study supports the idea that C-terminal residue of CCK is more important for biological potency than for binding to CCK receptors.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague.
authors.forename: L
authors.initials: L
authors.lastname: Maletínská
authors.forename: J
authors.initials: J
authors.lastname: Pírková
authors.forename: J
authors.initials: J
authors.lastname: Hlavácek
authors.forename: J
authors.initials: J
authors.lastname: Slaninová
mesh_terms: D000681:Amylases / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D000855:Anorexia / Q000139:chemically induced; D002490:Central Nervous System / Q000187:drug effects*; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D005704:Gallbladder / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism; D012890:Sleep / Q000187:drug effects
chemical_list: D018712:Analgesics, Non-Narcotic; D006993:Hypnotics and Sedatives; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D000681:Amylases