377727-87-2

Preladenant is an orally bioavailable antagonist of the adenosine A_2A receptor (K_is = 1.1 and 2.5 nM for human and rat receptors, respectively). It is selective for A_2A receptors over A₁, A_2B, and A₃ receptors (K_is = >1,000, >1,700, and >1,000 nM, respectively) as well as a panel of 59 receptors, enzymes, and ion channels. Preladenant inhibits adenylate cyclase activity (K_bs = 1.3 and 0.7 nM for human and rat receptors, respectively) induced by the A_2A receptor agonist CGS 21680 (Item No. 17126). It inhibits catalepsy induced by haloperidol (Item No. 12014) in rats by 77 and 70% after 1 and 4 hours, respectively, when administered at a dose of 1 mg/kg. Preladenant also increases the efficacy of L-DOPA (Item No. 13248) when used in combination with eltoprazine (Item No. 18428) in a 6-OHDA rat lesion model of Parkinson’s disease dyskinesia.

A potent and selective antagonist at the adenosine A2A receptor. It is being researched as a potential treatment for Parkinson's disease.

adenosine A2A receptor

1)?Hodgson?et al.?(2009), Characterization of the potent and selective A2A receptor antagonists preladenant and SCH 412348 [7-[2-[4-2,4-difluorophenyl]-1-piperazinyl]ethyl]-2-(2-furanyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimodin-5-amine] in rat models of movement disorders and depression;?J.Pharmacol.Exp.Ther.?330294 2)?Hodgson?et al.?(2010), Preladenant, a selective A(2A) receptor antagonist, is active in primate models of movement disorders;?Exp.Neurol.?225384 3)?Pinna?et al.?(2016), Antidyskinetic effect of A2A and 5HT1A/B receptor ligands in two animal models of Parkinson’s disease;?Mov.Disord.?31501 4)?Beavis?et al.?(2013), Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors;?Proc.Natl.Acad.Sci USA.?11014711 5)?Hatfield and Sitkovsky (2016), A2A adenosine receptor antagonist to weaken the hypoxia-HIF-1a driven immunosuppression and improve immunotherapies of cancer;?Curr.Opin.Pharmacol.?2990 6)?Ohta?et al.?(2016), A metabolic immune checkpoint: adenosine in the tumor microenvironment;?Front.Immunol.?71 7)?NCT03099161