Design, synthesis and biological evaluation of a bivalent micro opiate and adenosine A1 receptor antagonist.
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 A(1) adenosine and mu opiate receptors with a K(i) of 0.8+/-0.05 and 0.7+/-0.03 microM, respectively. This hybrid molecule increases cAMP production in cells that over express the mu receptor as well as those over expressing the A(1) adenosine receptor and reverses the antalgic effects of mu and A(1) adenosine receptor agonists in animals.
Mathew
Smitha C
SC
Aix-Marseille Université, Institut des Sciences Moléculaires de Marseille, iSm2-UMR CNRS 6263, Centre Saint Jérôme, Service 531, 13397 Marseille Cedex 20, France.
Ghosh
Nandita
N
By
Youlet
Y
Berthault
Aurélie
A
Virolleaud
Marie-Alice
MA
Carrega
Louis
L
Chouraqui
Gaëlle
G
Commeiras
Laurent
L
Condo
Jocelyne
J
Attolini
Mireille
M
Gaudel-Siri
Anouk
A
Ruf
Jean
J
Parrain
Jean-Luc
JL
Rodriguez
Jean
J
Guieu
Régis
R
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists; D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D008024:Ligands; D015394:Molecular Structure; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D058916:Adenosine A1 Receptor Antagonists; D000813:Anilides; D008024:Ligands; D017450:Receptors, Opioid, mu; D000241:Adenosine