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目的 观察新化合物L11对sigma-1受体的亲和力、受体功能的影响以及小鼠急性毒性、镇痛效应,为其药效和初步毒性评价提供实验依据.方法 采用体外受体结合和功能实验以及体内的小鼠急性毒性、福尔马林模型和大鼠坐骨神经慢性压迫损伤(chronic constriction injury, CCI)模型实验,分别测定L11对sigma-1受体的抑制率、功能和LD50、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-1,加入苯妥英(sigma-1受体变构调节剂)后的Ki值为8.10 nmol·L-1.L11小鼠灌胃LD50为1680.03 mg·kg-1,95% 的可信区间为(1559.35 ~1819.40)mg·kg-1.与模型组比较,L11可明显减少小鼠的II相舔抬足时间、增加大鼠的机械痛阈值(P<0.01).结论 新化合物 L11对 sigma-1受体有较高的亲和力,属于sigma-1受体的拮抗剂;L11灌胃毒性较小,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.“,”Aim To observe the effect of new com-pound L11 on the affinity and function of sigma-1 re-ceptor,as well as the mouse acute toxicity and analge-sic effect, so as to provide the experimental basis for its pharmacodynamics and preliminary toxicity evalua-tion. Methods Using binding and function test of sig-ma-1 receptor in vitro, the acute toxicity and formalin model test of mice,as well as the rat chronic constric-tion injury(CCI) model test in vivo,the effects of L11 on the inhibitory rate and function of sigma-1 receptor, LD50,lifting/licking time of mice and mechanical pain threshold of rats were respectively measured to evaluate the analgesic effect and mechanism of L11. Results The inhibitory rate and Kiof L11 on the sigma-1 recep-tor were 103.07% and 4.81 nmol·L-1,respectively. The Kivalue was 8.10 nmol·L-1while adding pheny-toin (sigma-1 receptor allosteric modulator). The in-tragastric administration of L11 in mice was 1 680.03 mg·kg-1LD50,and the 95% confidence interval was (1 559.35 ~1 819.40) mg·kg-1. Compared with model group, the II phase lifting/licking time of mice was significantly reduced and the mechanical pain threshold of rat obviously increased by L11. Conclu-sions The new compound L11 has high affinity to sig-ma-1 receptor, which belongs to the antagonist of sig-ma-1 receptor;L11 is less toxic to intragastric adminis-tration and has obvious analgesic effect on the formalin model of mice and CCI model of rats, which may be relative with the sigma-1 receptor antagonism.