目的 評價ig瑞格列汀對小鼠自主活動及協(xié)同睡眠的影響,以發(fā)現(xiàn)潛在非期望藥理作用。方法 將小鼠隨機(jī)分為4組,包括對照組和瑞格列汀10、20、40 mg/kg組,單次ig給予溶媒或供試品,進(jìn)行小鼠自主活動次數(shù)測定和協(xié)同睡眠影響分析。結(jié)果 ig給藥后,各組動物均未見異常,未出現(xiàn)行動遲緩、活動不協(xié)調(diào)等反應(yīng)。不同劑量組之間動物自主活動次數(shù)無明顯差異。在接受戊巴比妥鈉注射后,與對照組動物相比較,供試品給藥組動物的入睡率無顯著性差異。結(jié)論 ig瑞格列汀在40 mg/kg及其劑量以下對小鼠自主活動無顯著性影響,與閾下催眠劑量的戊巴比妥鈉合用無明顯協(xié)同催眠作用。研究結(jié)果為臨床進(jìn)一步評價其安全性奠定了基礎(chǔ)。

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"重大新藥創(chuàng)制"科技重大專項(2012ZX09302001)