四氢嘧啶类化合物PL-1215的镇痛作用及机制  

Antinociceptive effect of a tetrahydropyrimidine compound PL-1215and the underlying mechanism

作　　者：林嘉[1] 彭小彬[1] 谢健航 余传林[1] 雷林生[1] 

机构地区：[1]南方医科大学药学院,广州510515

出　　处：《中国科技论文》2016年第6期688-693,共6页China Sciencepaper

基　　金：高等学校博士学科点专项科研基金资助项目(20114433110013)

摘　　要：探讨1,3-二环戊基-1,2,3,6-四氢嘧啶-4,5-二甲酸二甲酯(PL-1215)的镇痛作用及机制,评估其应用前景。经灌胃(i.g.)给药,PL-1215(10、30、90mg/kg)能减少醋酸所致小鼠的扭体反应次数,延长小鼠热板致痛和大鼠甩尾反应的潜伏期。PL-1215(30mg/kg,i.g.)对扭体反应的抑制作用可被利血平所减弱,不被纳络酮所影响。PL-1215(30mg/kg,i.g.)可抑制由腹腔注射0.7%醋酸所致的小鼠脑干中5-羟色胺(5-hydroxytryptamine,5-HT)含量的下降。经PL-1215(100mg/kg,i.g.)长期处理小鼠,未出现明显戒断现象。总之,PL-1215的镇痛作用与脑中5-HT的功能有关,可考虑将其作为治疗轻度慢性疼痛的药物或将其作为先导化合物的进一步开发。The antinociceptive effect of 1,3-dicyclopentyl-l, 2,3,6-tetrahydro-pyrimidine-4,5-dicarboxylic acid dimethyl ester （PL- 1215） and the underlying mechanism were investigated and its application potential was evaluated. PL-1215 given orally doses of 10,30,90 mg/kg can produce significant inhibition on chemical nociception induced by intraperitoneal acetic acid injection and thermal nociception in the hot plate in mice or tail-flick test in rats. The inhibition of acetic acid-induced mouse writhing by PL- 1215 （30 mg/kg, i. g. ） is attenuated by reserpine, but not affected by naloxone. PL-1215 （30 mg/kg, i. g. ） inhibits the decrease of 5-hydroxytryptamine （5-HT） in mouse brainstem induced by intraperitoneal injection of 0. 7% acetic acid. Chronic administra-tion of mice with PL-1215 （100 mg/kg, i. g. ） does not result in obvious abstinence syndrome. It is suggested that 5-HT in brain is involved in analgesic action of PL-1215 and it may be developed for the treatment of mild chronic pain or used as a lead for further development.

关 键 词：药理学 镇痛药 四氢嘧啶 PL-1215 作用机制 5-羟色胺 

分 类 号：R965[医药卫生—药理学]