Study on dual-target novel analgesic small molecules based on σ1 receptor and μ receptor
OBJECTIVE To design and synthesize a series of small molecule compounds with dual σ1 and µ receptor interactions and to preliminarily investigate the neuropathic analgesic activities of different doses of these compounds on chronic sciatic nerve constriction(CCI)in rats.METHODS The target compounds Ⅰ a-Ⅰ c were prepared from bromo-benzene substituted by different groups through C-N coupling reaction and reduction amination reaction.110 rats were randomly divided into 11 groups(blank control group,positive control group,9 experimental groups).Each group consists of 10 rats.CCI model was prepared on the left hind leg.7 days after operation,the blank control group was treated with DMSO,the positive control group was treated with diclofenac sodium,and the experimental group were treated with different doses of target compounds,respectively.The paw withdrawal threshold was measured and compared at different time points before and after administration.RESULTS and CONCLUSION The target compounds Ⅰ a-Ⅰ c were synthesized.Their structures were confirmed by NMR and ESI-MS.Compared with before administration,DMSO had no significant effect on the mechanical pain threshold of rats,while the mechanical pain threshold was increased in the experimental groups with different doses.The analgesic effect may be enhanced with the increase of the dosage,but this effect may be not obvious when the dose exceeds a certain limit.CompoundsⅠ a and Ⅰ b showed better analgesic activity than Ⅰ c at medium and low doses,respectively,which provided a basis for further modification of dual-target analgesic drugs for neuropathic pain.
NETL
NSTL
万方数据
