The continuous sedative effects of a newly synthesized purine derivative WS070133 : is there any dif

来源 :第二届世界天然药物和传统药物药理学学术会议 | 被引量 : 0次 | 上传用户:guojiaguangdian
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  AIM In clinical practice, sedatives are expected to induce the continuum of sedation.We firstly combined a series of behavioral animal models to evaluate a new sedative candidate named WS070133 whether owned the continuous sedative effects.METHODS We used the elevated plus maze test to examine the minimal sedation (anxiolysis) ; the locomotor activity, hole-board and pentobarbital sodium induced hypnosis tests to evaluate the moderate sedation (twilight sleep) ; the tail flick test to investigate thodeepsedation (analgesia) ;the loss of righting reflex test to observe the general anesthesia.The influence of WS070133 on the memory and motor coordinationin normal mice was also observed.The determination of adenosine deaminase activity and adenosine level in the brain of mice as well as picrotoxin induced seizure testwere conducted to explore the mechanism.RESULTS WS070133 significandy increased the entries and time spent in open arms ; reduced head tips and locomotor activity counts; shortened the time to sleep,prolonged the sleeping time in pentobarbital sodium treated mice; increased pain threshold of normal mice in tail flick test; exerted non-anesthesia effect in the loss of righting reflex test.In contrary to diazepam, WS070133made no significant influence on the memory and motor coordinationlesion, did not protect miceagainst picrotoxin induced seizure, but inhibited adenosine deaminase activity and increased adenosine level in the cortex and hypothalamus of mice.CONCLUSION We firstly reported the continuous sedative effects from minimal sedation to deep sedation of WS070133.WS070133 lacked some side effects of diazepam and the mechanism underlying sedation was associated with adenosine system.
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