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KCNQ钾离子通道开放剂的筛选及抗癫痫活性观察
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作者 李佳 王远 +2 位作者 宋超 贾庆忠 祁金龙 《中国药理学通报》 CAS CSCD 北大核心 2024年第9期1744-1752,共9页
目的筛选KCNQ通道开放活性化合物并进一步评价其抗癫痫作用。方法利用铷流出高通量筛选技术初筛,对优选化合物QO-72,复制多个动物模型,通过行为学以及脑电图(EEG)分析,结合一般药理学实验,对其有效性安全性进行初步评价,并探讨作用机制... 目的筛选KCNQ通道开放活性化合物并进一步评价其抗癫痫作用。方法利用铷流出高通量筛选技术初筛,对优选化合物QO-72,复制多个动物模型,通过行为学以及脑电图(EEG)分析,结合一般药理学实验,对其有效性安全性进行初步评价,并探讨作用机制。结果得到3个系列活性化合物共51个。化合物QO-72在MES和PTZ急性实验中,灌胃和腹腔注射可明显提高抗惊厥保护率(P<0.05,0.01),延长癫痫大发作阈值(P<0.01)。在PTZ点燃慢性癫痫模型中,QO-72腹腔注射不同剂量均可降低癫痫发作等级(P<0.01),缩短癫痫发作持续时间(P<0.01),大剂量明显提高发作保护率(P<0.01);QO-72治疗组EEG癫痫波时程明显缩短、振幅明显降低、波功率谱密度明显下降(P<0.05,0.01)。QO-72灌胃给药治疗剂量16倍或腹腔注射8倍,对小鼠协调运动、自主活动、戊巴比妥钠协同睡眠无明显影响。QO-72给药组海马区脑脊液GABA含量可明显增加(P<0.01),Glu没有明显变化(P>0.05)。结论化合物QO-72在电刺激和化学诱导的急、慢性癫痫模型上,均表现出良好抗癫痫作用,其机制除开放KCNQ通道外,可能还与增加脑内抑制性神经递质GABA含量有关。 展开更多
关键词 癫痫 kcnq开放剂 高通量筛选 戊四唑 脑电图 一般药理学
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Development of high-performance liquid chromatography assay for pharmacokinetic analysis of KCNQ/M-channel opener QO58-lysin in rat plasma
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作者 马天阳 滕博川 +2 位作者 祁金龙 张海林 王克威 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2014年第3期153-158,共6页
A simple, reliable and efficient assay for quantitative analysis of a novel Kv7/KCNQ/M-channel opener QO58-lysin in rat plasma was developed using high-performance liquid chromatography(HPLC) with UV detection. Sepa... A simple, reliable and efficient assay for quantitative analysis of a novel Kv7/KCNQ/M-channel opener QO58-lysin in rat plasma was developed using high-performance liquid chromatography(HPLC) with UV detection. Separation of compound QO58-lysin from plasma was achieved using a reverse-phase C18 column with a mobile phase of 0.2 M ammonium acetate in H2O–acetonitrile(40:60, v/v) with nitrendipine used as an internal standard(IS). The retention times of QO58-lysin and the IS in rat plasma were 3.8 and 5.4 min, respectively. Calibration curve was linear ranging from 0.1 to 120 μg/mL with correlation coefficient(r2) of 0.9996. The lower limit of quantification was 0.1 μg/mL. Accuracy, precision, recovery as well as stability were all within acceptable criteria according to Food and Drug Administration(FDA) guidelines. This validated assay was successfully applied to determine the pharmacokinetics of QO58-lysin administered intravenously(10 mg/kg) in SD rats. The distribution and elimination half-life of QO58-lysin in plasma was(0.25±0.16) h and(2.15±0.12) h, respectively. 展开更多
关键词 kcnq opener QO58-lysin HPLC PHARMACOKINETICS
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