曲马朵与二氢埃托啡协同镇痛并推迟大鼠急性耐受(英文)  

Tramadol and dihydroetorphine produce synergistic analgesic effect and postpones acute opiate tolerance in rats

作　　者：明晓云 王巍 韩济生[1] 罗非[1] 

机构地区：[1]北京大学神经科学研究所北京大学基础医学院神经生物学系

出　　处：《生理学报》2005年第6期696-704,共9页Acta Physiologica Sinica

基　　金：This work was supported by the National Natural Science Foundation of China(No.39700188,30170307,and 30370461)the National Basic Research Priorities Programme of China(2001,No.50and2003CB515407)a grant from the 211 project,and a startup grant for young scientists from the 985 project of Peking University.

摘　　要：本文旨在研究曲马朵(tramadol,TRA)和二氢埃托啡(dihydroetorphine,DHE)联合用药是否可产生协同镇痛并延缓耐受的发生。TRA(mg,腹腔注射)与DHE(ng,皮下注射)按固定比率给药(1∶6．25,1∶12．5,1∶25,1∶50,1∶100,1∶200), 用热辐射甩尾法评价镇痛效应,采用等高线法评估药物的协同作用。在急性耐受实验中,连续6次注射TRA(20 mg／kg)、 DHE(1000 ng/kg)或两药的组合(TRA20 mg／kg+DHE 250 ng／kg)。结果显示:(1)除1 mg∶6．25 ng和1mg∶50 ng两个比例外, 其他所有比例用药均产生显著的协同镇痛效应;(2)TRA与DHE联合用药的疗效在连续给药中持续时间明显延长,提示二者联合使用可延缓耐受。以上结果提示:TRA与DHE在一定剂量比范围内可产生协同镇痛效应,并可推迟耐受的形成。The present study investigated whether a co-application of tramadol （TRA） and dihydroetorphine （DHE） would exert a synergy in analgesic effect and delay acute tolerance development. Intraperitoneal injection of TRA （in mg） and subcutaneous injection of DHE （in ng） were delivered in fixed proportions （1：6.25, 1：12.5, 1：25, 1：50, 1：100, and 1：200）. The effect of analgesia was accessed by tail-flick test and analyzed with isobolographic analysis. For test of acute tolerance, six successive injections of either TRA （20 mg/ kg） alone, DHE （1 000 ng/kg） alone, or a combination of TRA （20 mg/kg） and DHE （250 ng/kg） were administered. We found that （1） except for 1 mg： 6.25 ng and 1 mg： 50 ng, combinations, all the other ratios produced a significant synergy in their analgesic effect; （2） the effect of analgesia induced by repeated TRA plus DHE injections lasted significantly longer, indicating a slower onset of acute tolerance. These results indicate that TRA and DHE injections in certain dose ratios can induce synergistic analgesia, which is resistant against the development of acute tolerance.

关 键 词：曲马朵 二氢埃托啡 协同作用 镇痛 急性耐受 

分 类 号：R614[医药卫生—麻醉学]