Design, Synthesis and Biological evaluation of a bivalent μ opiate and adenosine A1 receptors antagonist

Smitha Mathew (1) , Nandita Ghosh (1) , Youlet By (2) , Aurélie Berthault (1) , Marie-Alice Virolleaud (1) , Louis Carrega (2) , Gaëlle Chouraqui (1) , Laurent Commeiras (1) , Jocelyne Condo (2) , Mireille Attolini (1) , Anouk Gaudel-Siri (1) , Jean Ruf (2) , Jean-Luc Parrain (1) , Jean Rodriguez (1) , Régis Guieu (2)

1 ISM2 - Institut des Sciences Moléculaires de Marseille
2 DS-ACI / UMR MD2 - Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques

The cross talk between different membrane receptors is the source of increasing research. We designed and synthesized a new hetero-bivalent ligand that has antagonist properties on both A1 adenosine and μ opiate receptors with a Ki of 0.8 ± 0.05 and 0.7 ± 0.03 μM, respectively. This hybrid molecule increases cAMP production in cells that over express the μ receptor as well as those over expressing the A1 adenosine receptor and reverses the antalgic effects of μ and A1 adenosine receptor agonists in animals.

Mots clés: Adenosine; Fentanyl; Bivalents antagonists; μ-Receptors; A1 receptors

Domaines: Chimie organique

Smitha Mathew, Nandita Ghosh, Youlet By, Aurélie Berthault, Marie-Alice Virolleaud, et al.. Design, Synthesis and Biological evaluation of a bivalent μ opiate and adenosine A1 receptors antagonist. Illustration. France. 2009. ⟨medihal-01727565⟩