目的 评价ig瑞格列汀对小鼠自主活动及协同睡眠的影响,以发现潜在非期望药理作用。方法 将小鼠随机分为4组,包括对照组和瑞格列汀10、20、40 mg/kg组,单次ig给予溶媒或供试品,进行小鼠自主活动次数测定和协同睡眠影响分析。结果 ig给药后,各组动物均未见异常,未出现行动迟缓、活动不协调等反应。不同剂量组之间动物自主活动次数无明显差异。在接受戊巴比妥钠注射后,与对照组动物相比较,供试品给药组动物的入睡率无显著性差异。结论 ig瑞格列汀在40 mg/kg及其剂量以下对小鼠自主活动无显著性影响,与阈下催眠剂量的戊巴比妥钠合用无明显协同催眠作用。研究结果为临床进一步评价其安全性奠定了基础。

Objective To investigate the effects of retagliptin on autonomic activities and synergy sleep of mice and its potential unexpected pharmacology. Methods Mice were randomly divided into control, 10, 20, and 40 mg/kg retagliptin groups. The animals were ig administered with vehicle control or test article. Then the number of mouse autonomic activities was detected and the effect on animal synergy sleep was analyzed. Results No abnormal reactions, such as slow behavior and discordant activity, were found in animals of all groups after treatment. There were no significant differences on autonomic activities of mice from different groups. Following injection with sodium pentobarbital, the sleeping rates of mice from test article-treated group was not different from the control group. Conclusion Our study indictes that the administration with 40 mg/kg or less retagliptin has no significant effect on autonomic activity and synergy sleep of mice against subthreshold hypnotic dose of sodium pentobarbita. These results will facilitate the further clinical safety study of retagliptin.

十二五"重大新药创制"科技重大专项(2012ZX09302001)