Experimental study on mouse acute toxicity and analgesic pharmacodynamics of new compound L11 / 中国药理学通报

ABSTRACT

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.