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New CCK2 agonists confirming the heterogeneity of CCK2 receptors: characterisation of BBL454

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Abstract

Pharmacological studies were undertaken with a new series of cholecystokinin2 CCK2 agonists in order to assign to them a CCK2A or CCK2B pharmacological profile. The open-field test was chosen as the discrimination test of CCK2B agonists. The most interesting agonist, BBL454 (0.03–300 μg/kg) induced hyperactivity which was blocked by a CCK2 antagonist, the D1 antagonist SCH23390, the δ-opioid antagonist naltrindole, but not a CCK1 antagonist. All compounds active in the open-field test are characterised by a common structural feature, –COCH2CO–Trp-NMeNle-Asp-Phe-NH2, whereas inactive compounds do not possess such a motive. Therefore, this feature can be considered crucial for CCK2B activity. BBL454 (0.03–3 μg/kg) improved memory in a two-trial memory test while it was very weakly active on the peripheral CCK2 receptor, and did not evoke anxiogenic effects in the plus-maze test. The synthesis of BBL454 is simple, its minimal active dose is 30 ng/kg and no “bell-shaped” responses were observed. These results suggest that BBL454 could be considered to be the new CCK2B reference agonist.

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Acknowledgements

We wish to thank Frédéric Etivant for multiform technical assistance, and Prof. B. P. Roques for accommodation in his laboratory.

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Author notes

  1. Bruno Bellier

    Present address: Section Analyse Chimique, Centre d’études du Bouchet, BP 3, 91710, Vert le Petit, France

  2. Christiane Garbay

    Present address: Laboratoire de Pharmacochimie Moléculaire et Cellulaire, Biomédicale des Saints Pères, U648 INSERM, FRE 2718 CNRS-UFR, 45, Rue des Saints Pères, 75270, Paris Cedex 06, France

Authors and Affiliations

  1. Laboratoire de Pharmacochimie Moléculaire et Structurale, Faculté des Sciences Pharmaceutiques et Biologiques, U266 INSERM, FRE 2463CNRS, 4, avenue de l’Observatoire, 75270, Paris Cedex 06, France

    Bruno Bellier, Dominique Crété, Marie-Emmanuelle Million, Françoise Beslot, Christiane Garbay & Valérie Daugé

  2. Unité de Neuroendocrinologie et Biologie Cellulaire digestives, Faculté de Médecine Xavier Bichat, U410 INSERM, 16, rue Henri Huchard, BP 416, 75870, Paris Cedex 18, France

    André Bado

  3. Neurobiologie et Psychiatrie, Faculté de Médecine, U513 INSERM, CHU Henri Mondor, 8 rue du Général Sarrail, Creteil, 94010, France

    Valérie Daugé

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  1. Bruno Bellier
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Correspondence to Valérie Daugé.

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Bellier, B., Crété, D., Million, ME. et al. New CCK2 agonists confirming the heterogeneity of CCK2 receptors: characterisation of BBL454. Naunyn-Schmiedeberg's Arch Pharmacol 370, 404–413 (2004). https://doi.org/10.1007/s00210-004-0969-7

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  • DOI: https://doi.org/10.1007/s00210-004-0969-7

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