Cutler S J, DeWitt Blanton C, Akin D T, Steinberg F B, Moore A B, Lott J A, Price T C, May S W, Pollock S H
Department of Pharmaceutical Sciences, Mercer University, Atlanta, GA 30341, USA.
Inflamm Res. 1998 Jul;47(7):316-24. doi: 10.1007/s000110050335.
1-(Carboxymethyl)-3,5-diphenyl-2-methylbenzene (CDB), a novel arylacetic acid, was evaluated in vivo for its ability to inhibit acute and chronic inflammation as well as acute pain.
The effects of CDB were evaluated using the following assays: 1) acute inflammation induced by the injection of carrageenan, bradykinin and serotonin into the subplantar region of the hind paw of rats; 2) chronic inflammation produced by the injection of Mycobacterium butyricum into the base of the tail of rats; 3) acute pain induced by the i.p. injection of phenyl-p-quinone into mice resulting in the production of writhes; 4) cyclooxygenase (COX) activity, including COX-1 and COX-2, evaluated using whole blood; and 5) activity of peptidylglycine alpha-monooxygenase (PAM) isolated from Xenopus laevis skin.
CDB (10 to 100mg/kg s.c.) produced a dose-dependent inhibition of carrageenan edema (ED50 of 41 mg/ kg at 3 h) which continued for up to 12 h. Using a therapeutic dosing regimen, this compound inhibited hind paw inflammation (>70%) and arthogram scores in rats with adjuvant-induced arthritis. This compound also possessed significant analgesic activity in mice (70% inhibition with 50mg/kg). CDB, however, lacked inhibitory activity on bradykinin and serotonin-induced edema. In addition, CDB significantly inhibited COX-I activity (IC50 approximately = 17 microM) while having only a weak inhibitory activity on both COX-2 and PAM activity.
CDB is an effective anti-inflammatory/analgesic agent whose mechanism of action appears to be associated with inhibition of COX-1 activity.
1-(羧甲基)-3,5-二苯基-2-甲基苯（CDB），一种新型芳基乙酸，对其抑制急性和慢性炎症以及急性疼痛的能力进行了体内评估。
使用以下试验评估CDB的作用：1）通过向大鼠后爪足底皮下注射角叉菜胶、缓激肽和5-羟色胺诱导急性炎症；2）通过向大鼠尾部基部注射丁酸分枝杆菌产生慢性炎症；3）通过腹腔注射苯基对苯醌诱导小鼠急性疼痛，导致扭体反应；4）使用全血评估环氧合酶（COX）活性，包括COX-1和COX-2；5）评估从非洲爪蟾皮肤分离的肽基甘氨酸α-单加氧酶（PAM）的活性。
CDB（10至100mg/kg皮下注射）对角叉菜胶性水肿产生剂量依赖性抑制（3小时时ED50为41mg/kg），持续长达12小时。采用治疗给药方案，该化合物可抑制佐剂诱导性关节炎大鼠的后爪炎症（>70%）和关节造影评分。该化合物在小鼠中也具有显著的镇痛活性（50mg/kg时抑制率为70%）。然而，CDB对缓激肽和5-羟色胺诱导的水肿缺乏抑制活性。此外，CDB显著抑制COX-1活性（IC50约为17μM），而对COX-2和PAM活性仅有微弱的抑制活性。
CDB是一种有效的抗炎/镇痛药，其作用机制似乎与抑制COX-1活性有关。
