In vitro and in vivo pharmacological characterization of two novel selective cannabinoid CB2 receptor inverse agonists

Some quinolone-3-carboxamides were previously shown to be selective ligands at cannabinoid CB2 receptors. We have performed here in vitro bioassays with the aim of investigating the functional activity of two such compounds, and have tested their potential analgesic actions in vivo. Both 2 and 3 behaved as CB2 inverse agonists in the [35S]GTPγS binding assay and decreased nociceptive behaviour in the late phase of the formalin test at the highest dose tested, whereas, at lower doses, they prevented the anti-nociceptive effects of a selective CB2 agonist in this test. These results identify in 2 and 3 two novel, potent and selective CB2 antagonists/inverse agonists.