Singh Vijay Pal, Patil Chandrashekhar S, Kulkarni Shrinivas K
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh - 160 014, India.
Fundam Clin Pharmacol. 2006 Feb;20(1):65-71. doi: 10.1111/j.1472-8206.2005.00387.x.
We investigated the pharmacological profile of licofelone [6-(4-chlorophenyl)-2,3-dihydro-2,2-dimethyl-7-phenyl-1H-pyrrolizine-5-acetic acid] against different inflammogens. The anti-inflammatory and anti-hyperalgesic effect of licofelone (2, 30 and 100 mg/kg, p.o.) against all the challenges was statistically significant (P < 0.05) when compared with control and indomethacin (10 mg/kg, p.o.). The ED(50) value of 19.1 mg/kg (onset by 2 h, duration: short), 13.0 mg/kg and 16.8 mg/kg (onset by 1 h, duration: long) was observed for licofelone against carrageenan-, arachidonic acid- and bradykinin-induced paw oedema, respectively. Similarly, licofelone showed ED(50) value of 47.6 mg/kg (onset by 1 h, duration: long), 92.2 mg/kg (onset by 1 h, duration: medium), and 78.6 mg/kg (onset by 2 h, duration: medium) against carrageenan-, arachidonic acid- and bradykinin-induced mechanical hyperalgesia, respectively. The rank order of potency based on percent inhibition and percent reversal against inflammation and mechanical hyperalgesia, respectively, was found to be licofelone > indomethacin. Moreover, licofelone (10-100 mg/kg, p.o.) significantly (P < 0.05) and dose-dependently prevented the Freund's adjuvant-induced increased vascularity in mice (vascularity index; 10 mg/kg: 0.059 +/- 0.015; 20 mg/kg: 0.048 +/- 0.004; 30 mg/kg: 0.039 +/- 0.012; 100 mg/kg: 0.025 +/- 0.015 vs. control: 0.0285 +/- 0.003). Furthermore, the results suggested that dual inhibitors of cyclooxygenase and lipoxygenase like licofelone provide an effective control of inflammation and hyperalgesia against acute inflammation/hyperalgesia in rats and mice.
我们研究了利考非洛[6-(4-氯苯基)-2,3-二氢-2,2-二甲基-7-苯基-1H-吡咯里嗪-5-乙酸]对不同炎症介质的药理特性。与对照组和吲哚美辛（10mg/kg,口服）相比，利考非洛（2、30和100mg/kg,口服）对所有刺激的抗炎和抗痛觉过敏作用具有统计学意义（P<0.05）。利考非洛对角叉菜胶、花生四烯酸和缓激肽诱导的爪肿胀的半数有效量（ED50）值分别为19.1mg/kg（起效时间2小时，持续时间：短）、13.0mg/kg和16.8mg/kg（起效时间1小时，持续时间：长）。同样，利考非洛对角叉菜胶、花生四烯酸和缓激肽诱导的机械性痛觉过敏的ED50值分别为47.6mg/kg（起效时间1小时，持续时间：长）、92.2mg/kg（起效时间1小时，持续时间：中等）和78.6mg/kg（起效时间2小时，持续时间：中等）。基于对炎症和机械性痛觉过敏的抑制百分比和逆转百分比，发现利考非洛的效价顺序为利考非洛>吲哚美辛。此外，利考非洛（10-100mg/kg,口服）显著（P<0.05）且剂量依赖性地抑制弗氏佐剂诱导的小鼠血管增生（血管增生指数；10mg/kg:0.059±0.015；20mg/kg:0.048±0.004；30mg/kg:0.039±0.012；100mg/kg:0.025±0.015，对照组为0.0285±0.003）。此外，结果表明，像利考非洛这样的环氧化酶和脂氧化酶双重抑制剂能有效控制大鼠和小鼠的急性炎症/痛觉过敏。
