a-740003

Description: A-740003 is a potent and selective P2X7 receptor antagonist. A-740003 has (IC(50) values = 40 nM for human and 18 nM for rat) as measured by agonist-stimulated changes in intracellular calcium concentrations. A-740003 showed weak or no activity (IC(50) > 10 muM) at other P2 receptors and an array of other neurotransmitter and peptide receptors, ion channels, reuptake sites, and enzymes. A-740003 potently blocked agonist-evoked IL-1beta release (IC(50) = 156 nM) and pore formation (IC(50) = 92 nM) in differentiated human THP-1 cells. A-740003 in vivo produces significant antinociception in animal models of neuropathic and inflammatory pain.

References: Janssen B, Vugts DJ, Funke U, Spaans A, Schuit RC, Kooijman E, Rongen M, PerkLR, Lammertsma AA, Windhorst AD. Synthesis and initial preclinical evaluation ofthe P2X7 receptor antagonist ¹¹CA-740003 as a novel tracer ofneuroinflammation. J Labelled Comp Radiopharm. 2014 Jun 30; 57(8):509-16. doi:10.1002/jlcr.3206. Epub 2014 Jul 3. PubMed PMID: 24995673.