JTE-907 [N-(benzo[1,3]dioxol-5-ylmethyl)-7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxamide] was evaluated in vitro and in vivo as a novel selective ligand for cannabinoid receptor of peripheral type (CB2). The compound binds with high affinity to human CB2 or mouse CB2 expressed on CHO cell membrane and to rat CB2 on splenocytes. The K(i) affinities for human, mouse, and rat CB2 were 35.9, 1.55, and 0.38 nM, respectively. The selectivity ratio for the CB2 receptors compared with central nervous type receptors (CB1) of human (expressed on CHO cells), and mouse and rat CB1 on cerebellum were 66, 684, and 2760, respectively. JTE-907 showed concentration-dependent increase of forskolin-stimulated cAMP production in CHO cells expressing human and mouse CB2 in vitro, i.e., JTE-907 behaved as an inverse agonist, which is in contrast to Win55212-2 that reduces cAMP as an agonist. JTE-907 dosed orally inhibited carrageenin-induced mouse paw edema dose dependently. The same in vivo effect was observed with other cannabinoid receptor ligands such as SR144528, Delta(9)-tetrahydrocannabinol (THC), and Win55212-2. This is the first report that a CB2-selective inverse agonist, JTE-907, has an anti-inflammatory effect in vivo, and how the inverse agonist showed the same effect as Win55212-2 and Delta(9)-THC is discussed.

中文翻译：

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JTE-907（大麻素CB2受体的新型选择性配体）的体外和体内药理学表征。

在体外和体内对JTE-907 [N-（苯并[1,3]二氧杂-5-基甲基）-7-甲氧基-2-氧杂-8-戊氧基-1,2-二氢喹啉-3-羧酰胺]进行了评估一种新型的外周型大麻素受体（CB2）选择性配体。该化合物与CHO细胞膜上表达的人CB2或小鼠CB2以及脾细胞上的大鼠CB2高亲和力结合。人，小鼠和大鼠CB2的K（i）亲和力分别为35.9、1.55和0.38 nM。与人（在CHO细胞上表达）和小脑上的小鼠和大鼠CB1相比，CB2受体与人的中枢神经型受体（CB1）的选择性比分别为66、684和2760。JTE-907在体外表达人和小鼠CB2的CHO细胞中显示出浓度依赖的毛喉素刺激的cAMP产生，即JTE-907表现为反向激动剂，与Win55212-2相比，后者减少了cAMP作为激动剂。JTE-907口服剂量依赖角叉菜胶诱导的小鼠爪水肿。使用其他大麻素受体配体（例如SR144528，Delta（9）-四氢大麻酚（THC）和Win55212-2）观察到相同的体内效果。这是第一份关于CB2选择性反向激动剂JTE-907在体内具有抗炎作用的报道，并讨论了该反向激动剂如何表现出与Win55212-2和Delta（9）-THC相同的作用。