三个环己醇类衍生物镇痛活性的研究

Studies on analgesic activities of the three cyclohexanol derivatives

目的 :本文对人工定向合成的三个胺基环己醇类衍生物 Fs- 812 5、Fs- 82 0 6、Fs- 870 2的镇痛活性进行研究 ,以期获得定向设计高效非成瘾性镇痛药物的可靠科学依据。方法 :用热板测痛法测定给药前和给药后 5～ 10 m in内的痛阈值 ,以 ED5 0值为比较对象 ,研究三个环己醇类衍生物对小白鼠的镇痛活性。结果 :1脑室给药 (ic)的镇痛 ED5 0 值显示 :Fs- 870 2 (ED5 0 值为1.8± 0 .6 2 ug· kg- 1 )的镇痛活性最强 ,而 Fs- 82 0 6略强于 Fs- 812 5 ,且二者无显著差别。 2腹腔给药 (ip)的 ED5 0 值。显示 Fs- 870 2镇痛活性最强 ,Fs- 812 5次之 ,Fs- 82 0 6最弱。 3ic/ip的比值提示 :Fs- 812 5的比值最大 ,脂溶性最强 ,最易通过血脑屏障 ,Fs- 870 2次之 ,Fs- 82 0 6的比值最小 ,最难通过血脑屏障。 4与吗啡的镇痛活性相比 ,Fs- 870 2为吗啡的 40倍 ,Fs-812 5和 Fs- 82 0 6都约为吗啡的 10倍。 5与吗啡的镇痛作用持续时间相比 ,Fs- 870 2最长 ,Fs- 82 0 6次之 ,Fs- 812 5最短。

Objective:The analgesic activities of the three synthetic cyclohexanol derivatives Fs- 81 2 5、Fs- 82 0 6、Fs- 870 2 were studied,in order to provide scientific basis for synthetizing a high、non- tolented anesthetics.methods:The pain threshold was determined before and 5～ 1 0 min after the drugs given by the hot- plate pain test.The analgesic activities was studied with the analgesic ED50 values in the rats.Results: 1 Analgesic ED50 values show thatthe Fs- 870 2 ( ED50 value is1 .8± 0 .62 ug·kg-1) is the strongestdrug in analgesic activities;and ic/ip values show that the Fs- 81 2 5can go through the Blood- Brain Barrier most easily than the other two derivatives.2 Compared with morphine the analgesic avtivity of the Fs- 870 2 is about 40 times stronger than that of Morphine;and the analgesic holding time of the Fs- 870 2 is the longest of the three derivaties and is48.3% of that of Morphine.