腺苷类似物WS090501的镇静、催眠和抗惊厥作用  

Sedative,hypnotic and anticonvulsive effects of an adenosine analogue WS090501

作　　者：李伟 张建军 

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,北京100050

出　　处：《药学学报》2011年第6期742-746,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30973512);国家“重大新药创制”科技重大专项(2009ZX09301-003,2008ZX09401-004)

摘　　要：腺苷是一种内源性的嘌呤核苷,具有广泛的生理性调节作用。腺苷类似物具有显著的镇静[1]、催眠和抗惊厥作用[2],可以抑制啮齿类动物的自主活动、诱导NREM睡眠（non rapid-eye-movement sleep,非快动眼睡眠）[3]。This study is to examine the sedative,hypnotic and anticonvulsive effects of an adenosine analogue,WS090501.The spontaneous locomotor activity was recorded by open field equipment,and the EEG of rats was recorded by polyphysiograph.Pentylenetetrazol（PTZ）-induced seizure model was used.The spontaneous locomotor activity was decreased by WS090501 at various doses（0.06,0.13,and 0.25 mg·kg-1）,and the decreasing rate was 28.4%,47.1% and 61.2% respectively.Furthermore,the effect of WS090501 on spontaneous locomotor activity of mice can be antagonized by DPCPX,a selective adenosine A1R antagonist,but cannot be antagonized by SCH58261,a selective adenosine A2AR antagonist.The NREM sleep was significantly increased by WS090501（0.05 and 0.2 mg·kg-1）,and the increasing rate was 27.6% and 102.8%,respectively,at 6th hour after administration.The REM sleep decreased significantly at the higher dose.PTZ induced serious convulsion in mice.The latency of convulsion was prolonged,and the number of seizure and mortality decreased after administration of WS090501.These results show that WS090501 has potent sedative,hypnotic and anticonvulsive effects,which may be mediated through adenosine A1R.

关 键 词：腺苷类似物 腺苷A1R 腺苷A2AR NREM睡眠 自主活动 

分 类 号：R965[医药卫生—药理学]