title: [Sedative, hypnotic and anticonvulsive effects of an adenosine analogue WS090501].
abstract: 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.
authors: 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.
authors: Wei
authors: W
authors: Li
authors: Jian-Jun
authors: JJ
authors: Zhang
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003292:Convulsants; D004569:Electroencephalography; D006993:Hypnotics and Sedatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010433:Pentylenetetrazole; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D012890:Sleep / Q000187:drug effects*; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000927:Anticonvulsants; D003292:Convulsants; D006993:Hypnotics and Sedatives; D011743:Pyrimidines; D014230:Triazoles; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D010433:Pentylenetetrazole