Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 370, Issue 5, pp 404–413

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

  • Bruno Bellier
  • Dominique Crété
  • Marie-Emmanuelle Million
  • Françoise Beslot
  • André Bado
  • Christiane Garbay
  • Valérie Daugé
Original Article

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.

Keywords

CCK2B receptor agonists BBL454 Open-field Memory Locomotor activity 

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Bruno Bellier
    • 1
    • 2
  • Dominique Crété
    • 1
  • Marie-Emmanuelle Million
    • 1
  • Françoise Beslot
    • 1
  • André Bado
    • 3
  • Christiane Garbay
    • 1
    • 4
  • Valérie Daugé
    • 1
    • 5
  1. 1.Laboratoire de Pharmacochimie Moléculaire et Structurale, Faculté des Sciences Pharmaceutiques et BiologiquesU266 INSERM, FRE 2463CNRSParis Cedex 06France
  2. 2.Section Analyse ChimiqueCentre d’études du BouchetVert le PetitFrance
  3. 3.Unité de Neuroendocrinologie et Biologie Cellulaire digestives, Faculté de Médecine Xavier BichatU410 INSERMParis Cedex 18France
  4. 4.Laboratoire de Pharmacochimie Moléculaire et Cellulaire, Biomédicale des Saints PèresU648 INSERM, FRE 2718 CNRS-UFRParis Cedex 06France
  5. 5.Neurobiologie et Psychiatrie, Faculté de MédecineU513 INSERM, CHU Henri MondorCreteilFrance

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