Li Wei, Zhang Jian-Jun
State Key Laboratory for Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Yao Xue Xue Bao. 2011 Jun;46(6):742-6.
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 x 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 x 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.
本研究旨在考察腺苷类似物WS090501的镇静、催眠和抗惊厥作用。通过旷场实验设备记录自发运动活动，并用多导生理记录仪记录大鼠脑电图。采用戊四氮（PTZ）诱导的癫痫模型。不同剂量（0.06、0.13和0.25mg·kg⁻¹）的WS090501均可降低自发运动活动，降低率分别为28.4%、47.1%和61.2%。此外，选择性腺苷A1R拮抗剂DPCPX可拮抗WS090501对小鼠自发运动活动的影响，而选择性腺苷A2AR拮抗剂SCH58261则不能。WS090501（0.05和0.2mg·kg⁻¹）可显著增加非快速眼动睡眠，给药后第6小时增加率分别为27.6%和102.8%。高剂量时快速眼动睡眠显著减少。PTZ可诱发小鼠严重惊厥。给药WS090501后惊厥潜伏期延长，癫痫发作次数和死亡率降低。这些结果表明WS090501具有强大的镇静、催眠和抗惊厥作用，其作用可能通过腺苷A1R介导。
