Development of new potent agonists able to interact with two postulated subsites of the cholecystokinin CCK-B receptor

Summary Since the biochemical and pharmacological profile of BC 197 and BC 264, two CCK₈-derived agonists with high specificity for CCK-B receptors, suggests their potential interaction with two CCK-B receptor subsites, it appeared essential to design new series of compounds that would be able to discriminate between these two subsites. As CCK₄ is the shortest fragment of CCK which interacts selectively with CCK-B receptors, compounds derived from the C-terminal tetrapeptide domain of BC 264, Boc-Trp-(NMe)Nle-Asp-Phe-NH₂, and of the cyclic compound BC 197, were prepared. While RB 360 (N-(cycloamido)-α-Me(R)Trp-(2S)-2-amino-9-((cycloamido)carbonyl)nonanoyl]-Asp-Phe-NH₂), like BC 197, has a CCK-B₁ profile with anxiogenic-like effects in the elevated plus-maze test, RB 400 (HOOC-CH₂-CO-Trp-(NMe)Nle-Asp-Phe-NH₂), like BC 264, seems to be a specific CCK-B₂ agonist, able to increase attention and/or memory processes in the Y-maze test.