新化合物L11与Sigma-1受体结合的特性及其镇痛药效学实验研究  

Experimental Study on Properties and Analgesic Pharmacodynamics of New Compound L11 Combined with Sigma-1 Receptor

作　　者：王蕊 汤道权[1] 

机构地区：[1]徐州医科大学药学院,江苏徐州221004 [2]江苏恩华药业股份有限公司,江苏徐州221002

出　　处：《抗感染药学》2017年第7期1284-1289,共6页Anti-infection Pharmacy

摘　　要：目的:研究新化合物L11对Sigma-1受体的亲和力、受体功能的影响及其镇痛效果,为其药效评价提供参考。方法:采用体外受体结合和功能实验以及体内的小鼠福尔马林模型和大鼠慢性坐骨神经压迫损伤(chronic constriction injury,简称CCI)模型实验,分别测定和分析L11对Sigma-1受体的抑制率、功能和福尔马林模型小鼠的舔足时间、CCI模型大鼠机械痛阈值的影响。结果:L11对Sigma-1受体的抑制率和Ki值分别为103.07%和4.81 nmol/L,加入苯妥英(Sigma-1受体变构调节剂)后的Ki值为8.10 nmol/L;与模型组比较,L11可显著减少小鼠的Ⅱ相舔抬足时间(P<0.01),增加了大鼠的机械痛阈值(P<0.01),对大鼠自主活动无明显影响。结论:新化合物L11对Sigma-1受体具有较高的亲和力,属于Sigma-1受体的拮抗剂,对小鼠福尔马林模型和大鼠CCI模型有明显的镇痛作用,其机制可能是通过Sigma-1受体而发挥镇痛作用。Objective： To study the properties and analgesic pharmacodynamics of new compound L11 combined with Sigma-1 receptor, and to provide a reference forits efficacy evaluation. Methods： Using binding and function test of Sigma-1 receptor in vitro, the mouse formalin model test and the rat chronic constriction injury （CCI） model test in vivo, the effects of L11 on the inhibition rate and function of Sigma-1 receptor, lifting/licKing time of mice and mechanical pain threshold of rat were respectively measured to evaluate the analgesic effect and mechanism of L11. Results： The inhibition rate and Ki of L11 on the Sigma- 1 receptor were 103.07% and 4.81 nmol/L, respectively. The Ki value was 8.10 nmol/L while adding phenytoin（Sigma-1 receptor allosteric modulator）. Compared with model group, the Ⅱ phase lifting/licKing time of mice was significantly reduced and the mechanical pain threshold of rat was obviously increased by L11, but the spontaneous activities of rat were not obviously changed by L11. Conclusion： The new compound L11 has high affinity to Sigma- 1 receptor, which belongs to the antagonist of Sigma- 1 receptor, and has obvious analgesic effect on the formalin model of mice and CCI model of rat; all these may be relative with the Sigma-1 receptor antagonism.

关 键 词：L11 Sigma-1受体 福尔马林模型 大鼠慢性压迫损伤模型 镇痛作用 

分 类 号：R965[医药卫生—药理学]