Pharmacological evaluation of 1-(carboxymethyl)-3,5-diphenyl-2-methylbenzene, a novel arylacetic acid with potential anti-inflammatory properties.
Pharmacological evaluation of 1-(carboxymethyl)-3,5-diphenyl-2-methylbenzene, a novel arylacetic acid with potential anti-inflammatory properties.
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1-(羧甲基)-3,5-二苯基-2-甲基苯的药理学评价，一种具有潜在抗炎特性的新型芳基乙酸。
DOI：
10.1007/s000110050335
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Pollock,SH
中科院分区：
文献类型：
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作者：
Cutler,SJ;DeWittBlantonJr,C;Akin,DT;Steinberg,FB;Moore,AB;Lott,JA;Price,TC;May,SW;Pollock,SH
目的研究新型芳基乙酸乙酯(Design:1-(Carboxymethyl)-3，5-diphenyl-2-methylbenzene，CDB)对急性和慢性炎症及急性疼痛的抑制作用。材料与方法：1)大鼠足底注射角叉菜胶、缓激肽和5-羟色胺所致的急性炎症反应；(2)大鼠尾底部注射丁酸分枝杆菌所致的慢性炎症反应；(3)大鼠ip所致的急性疼痛反应。4)环氧合酶(COX)活性，包括COX-1和COX-2；5)从非洲爪哇皮多肽甘氨酸α-单加氧酶(PAM)的活性。对角叉菜胶肿胀有剂量依赖性抑制作用(ED50为41 mg/kg，3 h)，持续12 h。采用治疗性给药方案，该化合物可抑制佐剂性关节炎大鼠的后爪炎(70%)和关节图评分。该化合物对小鼠也有明显的镇痛作用(50 mg/kg时抑制率为70%)。然而，CDB对缓激肽和5-羟色胺引起的水肿缺乏抑制活性。此外，CDB还能显著抑制COX-1活性(IC50≅ 17 μM)，而对COX-2和PAM活性只有微弱的抑制作用。？结论：CDB是一种有效的抗炎镇痛药，其作用机制可能与抑制COX-1活性有关。
Objective and Design: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.¶Materials and Methods: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 ofMycobacterium butyricuminto 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 α-monooxygenase (PAM) isolated fromXenopus laevisskin.¶Results:CDB (10 to 100 mg/kg s.c.) produced a dose-dependent inhibition of carrageenan edema (ED50of 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 50 mg/kg). CDB, however, lacked inhibitory activity on bradykinin and serotonin-induced edema. In addition, CDB significantly inhibited COX-1 activity (IC50≅ 17 μM) while having only a weak inhibitory activity on both COX-2 and PAM activity.¶Conclusions:CDB is an effective anti-inflammatory/analgesic agent whose mechanism of action appears to be associated with inhibition of COX-1 activity.