苦远胶囊的药理学研究
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摘要
目的:考察苦远胶囊的镇静、催眠作用,为开发出一种疗效好,毒性小,质量可控的治疗失眠的中药新药提供实验依据。
方法:通过采用特异的药效学跟踪实验来确定苦远胶囊的最佳处方及最佳提取工艺;对苦远胶囊进行急性毒性实验,利用Bliss法得出苦远胶囊的LD50并计算出其95%可信限;通过苦远胶囊对小白鼠自主活动的影响,对小白鼠戊巴比妥钠阈下催眠剂量作用的影响,对小白鼠延长戊巴比妥钠催眠时间的影响以及对正常大鼠睡眠脑电图(EEG)的分析,将行为学观察法与神经电生理实验方法结合起来对苦远胶囊进行药效学研究。
结果:
1.处方2组能显著增加小白鼠翻正反射消失数(P<0.01),处方1组可显著缩短阈剂量戊巴比妥钠所致小白鼠睡眠的入睡潜伏期,并能延长小白鼠的睡眠时间(P<0.05),采用综合评分法对实验结果进行综合评定,以得分高者为最佳处方,最终确定苦远胶囊的最佳处方为处方2。
2.工艺1组和工艺4组均能显著增加小白鼠翻正反射消失数(P<0.05),工艺2组可显著延长阈剂量戊巴比妥钠所致小白鼠睡眠的睡眠时间(P<0.01),工艺4组可显著缩短阈剂量戊巴比妥钠所致小白鼠睡眠的入睡潜伏期,并能延长小白鼠的睡眠时间(P<0.05)。综合以上的实验结果,确定工艺4为苦远胶囊的最佳提取工艺。
3.苦远胶囊小白鼠口服灌胃给药LD50为42.61g/kg,其95%可信限为36.97～49.10g/kg。
4.苦远胶囊中、高剂量组能够明显地减少小白鼠的自主活动次数(P<0.05);苦远胶囊低、中、高剂量组均能显著增加小白鼠翻正反射消失数(P<0.01);苦远胶囊中、高剂量组可显著延长阈剂量戊巴比妥钠所致小白鼠睡眠的睡眠时间(P<0.05);苦远胶囊高剂量组能显著延长正常大鼠睡眠时相中的SWS1期,并且能够显著增加脑电波中δ波的百分比(P<0.01),表明高剂量的苦远胶囊对正常大鼠的睡眠脑电波具有改善作用。
结论:
1.苦远胶囊的最佳处方为处方2。
2.苦远胶囊的最佳提取工艺为工艺4。
3.苦远胶囊小白鼠口服灌胃给药LD50为42.61g/kg,其95%可信限为36.97～49.10g/kg。
4.药效学实验表明苦远胶囊具有较好的镇静、催眠作用。
Purpose:The purpose is to investigate the sedation and hypnosis effect of Kuyuan capsule.The topic will provide an experimental evidence for new TCM drugs in treating insomnia which with definite material basis,good efficacy,low toxicity,and controllable quality.
Method:This research subject through the special pharmacodynamics tracking test to determine the best prescription and the optimum extraction process. Detect median lethal dose(LD50) and the confidence limit of 95% of Kuyuan capsule by the bliss method. Through the effect of Kuyuan capsule on locomotor activity in mice,the effect on mice hypnosis of pentobarbital sodium of subthreshold dosage,the hypnotic time experiment on mice by pentobarbital sodium in threshold dosage and the analysis of electroencephalogram on rats,we carry out the pharmacodynamic study of Kuyuan capsule with the behavior experiments and electrophysiological techniques.
Results:
1.Prescription No.2 could enhance the number of asleep mice of pentobarbital sodium in subthreshold hypnotic dosage(P<0.01).Prescription No.1 could shorten substantially the rats' sleep latent period and prolong obviously the rats' sleep time which induced by pentobarbital sodium at threshold dosage(P<0.05). Prescription No.2 was certified as the optimal prescription by using comprehensive scoring method.
2.Process No.1 and No.4 drug group could enhance the number of asleep mice of pentobarbital sodium in subthreshold hypnotic dosage(P<0.05), process No.2 drug group could prolong obviously the rats' sleep time which induced by pentobarbital sodium at threshold dosage(P<0.01),process No.4 drug group could shorten substantially the rats' sleep latent period and prolong obviously the rats' sleep time which induced by pentobarbital sodium at threshold dosage (P<0.05). The results showed that process No.4 was the optimal process.
3.The median lethal dose(LD50) of Kuyuan capsule was 42.61g/kg.The confidence limit of 95% was 36.97～49.10g/kg.
4.The middle dosage and high dosage of Kuyuan capsule could significantly inhibit the locomotor activity in mice(P<0.05).Low dosage, middle dosage and high dosage of Kuyuan capsule could enhance the number of asleep mice of pentobarbital sodium in subthreshold hypnotic dosage(P<0.01). Middle dosage and high dosage of Kuyuan capsule could prolong obviously the rats' sleep time which induced by pentobarbital sodium at threshold dosage(P<0.05).The experimental results indicated that contribution to sleep phase of the normal rats,SWS1 and the percentage of brain wave(δ)(P<0.01)of the normal rats were all significantly prolonged after administration of high dosage of Kuyuan capsule.
Conclusion:
1.Prescription No.2 was certified as the optimal prescription of Kuyuan capsule.
2.Process No.4 was the optimal process of Kuyuan capsule.
3.The median lethal dose(LD50) of Kuyuan capsule was 42.61g/kg.The confidence limit of 95% was 36.97～49.10g/kg.
4.Pharmacodynamics proves that Kuyuan capsule really has hypnotic and sedative effects.
方法:通过采用特异的药效学跟踪实验来确定苦远胶囊的最佳处方及最佳提取工艺;对苦远胶囊进行急性毒性实验,利用Bliss法得出苦远胶囊的LD50并计算出其95%可信限;通过苦远胶囊对小白鼠自主活动的影响,对小白鼠戊巴比妥钠阈下催眠剂量作用的影响,对小白鼠延长戊巴比妥钠催眠时间的影响以及对正常大鼠睡眠脑电图(EEG)的分析,将行为学观察法与神经电生理实验方法结合起来对苦远胶囊进行药效学研究。
结果:
1.处方2组能显著增加小白鼠翻正反射消失数(P<0.01),处方1组可显著缩短阈剂量戊巴比妥钠所致小白鼠睡眠的入睡潜伏期,并能延长小白鼠的睡眠时间(P<0.05),采用综合评分法对实验结果进行综合评定,以得分高者为最佳处方,最终确定苦远胶囊的最佳处方为处方2。
2.工艺1组和工艺4组均能显著增加小白鼠翻正反射消失数(P<0.05),工艺2组可显著延长阈剂量戊巴比妥钠所致小白鼠睡眠的睡眠时间(P<0.01),工艺4组可显著缩短阈剂量戊巴比妥钠所致小白鼠睡眠的入睡潜伏期,并能延长小白鼠的睡眠时间(P<0.05)。综合以上的实验结果,确定工艺4为苦远胶囊的最佳提取工艺。
3.苦远胶囊小白鼠口服灌胃给药LD50为42.61g/kg,其95%可信限为36.97～49.10g/kg。
4.苦远胶囊中、高剂量组能够明显地减少小白鼠的自主活动次数(P<0.05);苦远胶囊低、中、高剂量组均能显著增加小白鼠翻正反射消失数(P<0.01);苦远胶囊中、高剂量组可显著延长阈剂量戊巴比妥钠所致小白鼠睡眠的睡眠时间(P<0.05);苦远胶囊高剂量组能显著延长正常大鼠睡眠时相中的SWS1期,并且能够显著增加脑电波中δ波的百分比(P<0.01),表明高剂量的苦远胶囊对正常大鼠的睡眠脑电波具有改善作用。
结论:
1.苦远胶囊的最佳处方为处方2。
2.苦远胶囊的最佳提取工艺为工艺4。
3.苦远胶囊小白鼠口服灌胃给药LD50为42.61g/kg,其95%可信限为36.97～49.10g/kg。
4.药效学实验表明苦远胶囊具有较好的镇静、催眠作用。
Purpose:The purpose is to investigate the sedation and hypnosis effect of Kuyuan capsule.The topic will provide an experimental evidence for new TCM drugs in treating insomnia which with definite material basis,good efficacy,low toxicity,and controllable quality.
Method:This research subject through the special pharmacodynamics tracking test to determine the best prescription and the optimum extraction process. Detect median lethal dose(LD50) and the confidence limit of 95% of Kuyuan capsule by the bliss method. Through the effect of Kuyuan capsule on locomotor activity in mice,the effect on mice hypnosis of pentobarbital sodium of subthreshold dosage,the hypnotic time experiment on mice by pentobarbital sodium in threshold dosage and the analysis of electroencephalogram on rats,we carry out the pharmacodynamic study of Kuyuan capsule with the behavior experiments and electrophysiological techniques.
Results:
1.Prescription No.2 could enhance the number of asleep mice of pentobarbital sodium in subthreshold hypnotic dosage(P<0.01).Prescription No.1 could shorten substantially the rats' sleep latent period and prolong obviously the rats' sleep time which induced by pentobarbital sodium at threshold dosage(P<0.05). Prescription No.2 was certified as the optimal prescription by using comprehensive scoring method.
2.Process No.1 and No.4 drug group could enhance the number of asleep mice of pentobarbital sodium in subthreshold hypnotic dosage(P<0.05), process No.2 drug group could prolong obviously the rats' sleep time which induced by pentobarbital sodium at threshold dosage(P<0.01),process No.4 drug group could shorten substantially the rats' sleep latent period and prolong obviously the rats' sleep time which induced by pentobarbital sodium at threshold dosage (P<0.05). The results showed that process No.4 was the optimal process.
3.The median lethal dose(LD50) of Kuyuan capsule was 42.61g/kg.The confidence limit of 95% was 36.97～49.10g/kg.
4.The middle dosage and high dosage of Kuyuan capsule could significantly inhibit the locomotor activity in mice(P<0.05).Low dosage, middle dosage and high dosage of Kuyuan capsule could enhance the number of asleep mice of pentobarbital sodium in subthreshold hypnotic dosage(P<0.01). Middle dosage and high dosage of Kuyuan capsule could prolong obviously the rats' sleep time which induced by pentobarbital sodium at threshold dosage(P<0.05).The experimental results indicated that contribution to sleep phase of the normal rats,SWS1 and the percentage of brain wave(δ)(P<0.01)of the normal rats were all significantly prolonged after administration of high dosage of Kuyuan capsule.
Conclusion:
1.Prescription No.2 was certified as the optimal prescription of Kuyuan capsule.
2.Process No.4 was the optimal process of Kuyuan capsule.
3.The median lethal dose(LD50) of Kuyuan capsule was 42.61g/kg.The confidence limit of 95% was 36.97～49.10g/kg.
4.Pharmacodynamics proves that Kuyuan capsule really has hypnotic and sedative effects.
引文
[1]杨玉龙.失眠的研究现状.中华实用中西医杂志.2005,(18):228-229.
[2]张宏,杜桂林,李显华,等.安眠颗粒治疗失眠的药效学研究.中药药理与临床.2003,19(2):42-43.
[3]顾晓路,梁茂新.安眠颗粒结构优化的步骤与方法.中国实验方剂学杂志.2008,14(6):22-26.
[4]游国雄,竺士秀,张可经.失眠与睡眠障碍疾病.北京:人民卫生出版社,2000:31.
[5]库宝善.改善睡眠药物开发新构想.生理科学进展.1992,23(2):107.
[6]张登本.中医神经精神病学[M].北京:中国医药科技出版社,2000:162-174.
[7]方药中,邓铁涛,李克光,等.实用中医内科学[M].上海:上海科学技术出版社,1989:345-349.
[8]高东艮.中医对睡眠与失眠的认识[J].中国中医基础医学杂志.1997,3:14-15.
[9]游国雄,竺士秀,张可经.失眠与睡眠障碍疾病[M] .北京:人民军医出版社.2000:1-5.
[10]刘平,兰胜作.失眠症临床检查与最佳治疗方案[M].天津:天津科学技术出版社,2002:14-17.
[11]罗和古.失眠[M].北京:中国医药科技出版社,2005:4-10.
[12]伍国锋,张文渊.脑电波产生的神经生理机制.临床脑电学杂志.2000,9(3) :188-190.
[13]佩雷兹·拉维.脑电波·睡眠之谜——一个魔幻的世界.上海:上海科学技术出版社,2001:12-13.
[14]赵忠新.临床睡眠障碍学[M].上海:第二军医大学出版社,2003:1-4.
[15]齐凤琴.具有改善睡眠作用药物的药效评价方法的建立:(硕士学位论文).哈尔滨:黑龙江中医药大学,2005.
[16]JOHN R.HUGHES.临床实用脑电图学[M].北京:人民卫生出版社,1999:51-58.
[17]张杰,王明时.睡眠脑电的研究[J].国外医学生物医学工程分册.1997,20(2):65-68.
[18]库宝善.慢波睡眠的药理学研究.北京医科大学学报.1999,31(3):204-208.
[19]李仪奎.中药药理实验方法学(第二版).上海:上海科学技术出版社,2006:217-227.
[20]徐叔云,卞如濂,陈修.药理实验方法学(第三版).北京:人民卫生出版社,2002:802-804.
[21]陈奇.中药药理研究方法学.北京:人民卫生出版社,1993:660-672.
[22]方文贤.中药药理研究实验设计浅析.中国中药杂志.1996,121(6):361-363.
[23] H.G.沃格尔,W.H.沃格尔.催眠作用药理学实验指南--新药发现和药理学评价.北京:科学技术出版社,2001:356.
[24]李树新,李中华,库宝善.家兔睡眠时相分析方法的建立.中国药理学通报.1996,12(5):429-430.
[25]靳照宇,库宝善,姚海燕,等.一种新的大鼠睡眠自动分析系统.中国药理学通报.1999,15(5):411-414.
[26]王绪平.苦参的镇静催眠作用研究:(硕士学位论文).杭州:浙江大学,2004.
[27]丁虹,乔文建.单胺类神经递质测定方法的研究.化学传感器.1992,12(2):14-19.
[28]匡培根.神经系统疾病药物治疗学[M].北京:人民卫生出版社,2002:1002.
[29]赵忠新,张红菊,黄流清.失眠的治疗药物及其使用方法研究进展.中国新药与临床杂志.2007,26(ll):851-856.
[30]靳元慧,曹玉凤,王金荣,等.浅谈失眠及镇静催眠药.中国执业药师.2006,(9):37-38.
[31]王泽民,王建女.睡眠障碍治疗药物的应用状况与评价[J] .医药导报.2005,(3):238.
[32]台大力,胡文祥,潭生建,等.催眠药研究进展[J].中国临床药学杂志.1998,7(4):195-197.
[33]刘郁.催眠镇静类药物的不良反应[J].辽宁医学杂志.2001,15(6):282-284.
[34] Wagner J,Wagner ML,Hening WA.Beyond benzo2 diazepines:alter native Pharmacologic agents for the treatment of insomnia[J].AnnPharm acother.1998,32(6):680-691.
[35] Maczaj M.Pharmacological treatment of insomnia[J].Drugs.1993,45(1):44-55.
[36]耿群美,李兰城,贾小英.苦参碱氧化苦参碱对小鼠脑中r-氨基丁酸和甘氨酸含量的影响[J].内蒙古医学杂志.1993,13(1):3.
[37]石京山,黄彬,吴芹,等.钩藤碱对小鼠活动和大鼠脑内的5-羟色胺及多巴胺影响[J].中国药理学报.1993,14(2):114.
[38]刘国卿,袁惠南,谢林,等.槐果碱等苦豆子生物碱对大鼠单胺代谢及多巴胺和5-羟色胺受体作用[J].药学学报.1987,(22):645.
[39]余建强,蒋袁絮,彭建中.氧化槐定碱对小鼠神经系统的影响[J].广东医学.2001,22(8):577.
[40]陈先瑜.秦艽生物碱药理作用(Ⅳ)对中枢神经系统作用[J].中药药理与临床.1992,8(5):45.
[41]马志清,刘国卿,霍小萍,等.左旋千金藤碱的中枢抑制作用[J].中国药科大学学报.1990,21(2):107.
[42]彭建中,金丽容,陈先瑜,等.脑室注射山莨菪碱、阿托品、樟柳碱和东莨菪碱的中枢作用[J].中国药理学报.1983,4(2):81.
[43]陈淑清,陈淑杰,刘健,等.不同产地黄连的体外抑菌活性与镇静作用[J].华西药学杂志.1990,5(3):168.
[44]周远鹏,江京莉.附子的研究(VI)附子中乌头碱及有关化合物的药理作用[J].中药药理与临床.1992,8(5):45.
[45]季宇彬,王月兰,台宝山,等.问荆碱对大鼠脑囊泡膜Mg2+-ATPase、Ca2+-ATPase抑制作用的动力学研究[J].中国中药杂志.1996,21(1):42.
[46]裴印权,岳微,崔景荣,等.胡椒碱衍生物的中枢药理作用研究[J].药学学报.1980,15(4):198.
[47]戴淑芳,高广猷.乌苏里藜芦碱对中枢神经系统的抑制作用[J].大连医科大学学报.1997,19(1):11.
[48]Rinura.Y. Studies on Scutellariae Radix[J].ChemPharm Bull.1981,29(8):2308.
[49]崔志清,王国祥,王立斌,等.雪莲黄酮甙A1对小鼠中枢神经系统作用[J].中草药.1995,26(5):247.
[50]高基铭,袁秉祥,李生正,等.淫羊藿总黄酮对家兔血小板功能及小鼠镇静、催眠及耐力作用的影响[J].西北药学杂志.1992,7(3):15.
[51]郭胜民,范晓霞,何建伟.酸枣仁总黄酮的中枢抑制作用[J].中药材.1998,21(11):578.
[52]汤臣康.五味子的化学和药理研究新进展[J].西北药学杂志.1994,9(6):279.
[53]连其琛,胡晓,上官珠,等.蛇床子素镇静作用的研究[J].中药新药与临床药理.2000,11(4):244.
[54]姜秀莲,曲淑岩,王一华,等.瑞香素对CNS的抑制作用[J].中药通报.1986,11(3):封2.
[55]顾健,胡锦官.石菖蒲及有效成分对中枢神经系统作用的实验研究[J].中药药理与临床.1999,15(3):19.
[56]张安平,陈敏珠,徐淑云.白芍总甙对大白鼠睡眠节律的影响[J].中药药理学通报. 1993,9(6):454.
[57]Honda.G.Isolation of Sedative Principles From Perilla Fruteslens[J].Chem Pharm Bull.1986,34(4):1672.
[58]郝洪谦,孙兵,郑开俊,等.郁金二酮对家猫睡眠节律电活动的调制作用[J].中草药.1994,25(8):423.
[59]王晖,许亚铭,王宗锐.薄荷醇对戊巴比妥中枢抑制作用的影响[J].现代应用药学.1995,12(3):1.
[60]齐治,田珍,秦玉香,等.糙叶败酱挥发油镇静作用的研究[J].天然产物研究与开发.1989,1(1):82.
[61]马越美,齐治,崔景荣,等.异叶败酱挥发油镇静作用的研究[J].中西医结合杂志.1987,7(11):671.
[62]池田正树.生姜的药理研究[J].国外医学·中医中药分册.1981,(2):53.
[63]于澍仁,尤胜权.芹菜甲素与乙素的抗惊厥作用[J].药学学报.1984,(8):566.
[64]吴尚霖,袁秉祥,马志义.酸枣仁油长期使用对小鼠催眠作用的影响[J].西北药学杂志.2001,15(3):114.
[65]胡盛珊,王大元,邱萍,等.枳实有效成分的药理活性比较[J].中草药.1994,25(8):419.
[66]周慧秋,于滨,乔婉红,等.甲基丁香酚药理作用研究[J].中医药学报.2000,28(2):79.
[67]沈雅琴,陈光娟,马树德,等.藁本中性油的镇静、镇痛、解热和抗炎作用[J].中西医结合杂志.1987,7(12):738.
[68]铃木幸子.丹皮酚的中枢作用[J].国外医学·中医中药分册.1983,(5):54.
[69]原田正敏.桂皮的药理学的研究(第一版)Cinnamaldehyde.中枢作用[J].药学杂志.1972,92(2):135.
[70]卞如濂.荆芥油的药理研究[J].浙江医科大学学报.1981,10(5):219.
[71]张罗修,余方考,郑秋影,等.雷公藤红素抑制抗体形成及抗炎作用[J].药学学报.1990,25(8):573.
[72]郭胜民,范晓霞,宋少刚,等.酸枣仁总皂甙中枢抑制作用研究[J].西北药学杂志.1996,11(4):166.
[73]倪小虎,杨柳,吕育齐,等.人参根及茎叶皂甙对群养及隔离孤独饲育小鼠神经药理作用的研究[J].中草药.1999,30(3):193.
[74]冯冰虹,孟青,郭晓玲,等.绞股蓝皂甙SH-6对脑内单胺递质及代谢产物的影响[J].中药新药与临床药理.1998,9(2):87.
[75]孙兵,郝洪谦,郑开俊,等.柴胡皂甙对猫睡眠节律电活动调制的实验研究[J].中草药.1994,25(2):82.
[76]高广猷,李传勋.山麦冬总皂甙对中枢神经系统抑制作用[J].中药药理与临床.1990,6(1):35.
[77]邝荔香.九子参总皂甙药理研究[J].时珍国医国药.1999,10(7):492.
[78]高勃.木总皂甙的中枢抑制作用[J].第四军医大学学报.1988,9(l):55.
[79]田新英,董承统.促睡眠植物提取液调节大鼠觉醒-睡眠周期的研究[J].脑与神经疾病杂志.2003,01(l):36-38.
[80]Claude Gottesmann,The transition from slow-wave sleep to paradoxical sleep:evolving facts and concepts of the neurophysiological processes underlying the intermediate stage of sleep[J].Neuroscience and Biobehavioral Reviews.1996,20(3):367-387.
[81]Youssef Slisli,Renaudde Beaurepaire.Interleukin-βand calcitonin,but not corticotropin-releasing factor,alter sleep cycles when injected into the rat hypothalamic lateral paraventricular area[J]. Neuroscience Letters.1999,265(4): 29-32.
[82]Pierre Gauthier,Christian Arnaud,Gabriel Gandolfo,etal.Influence of GABAB receptor antagonist on the sleep-waking cycle in the rat[J].BrainResearch.1997, 773(10):8-14.
[83]M.Yoshimoto,H.Higuchi,M.Kamata,etal.The effects of benzodiazepine (triazolam),cyclpyrrolone (zopiclone) and imidazopyridine (zolpidem) hypnoticson the frequence of hippocampal theta activityand sleep structure in rats[J]. European Neuropsychopharmacology.1999,9(1):29-35.
[84]Koichi Saitou,Yoshio Kaneko,Yukio Sugimoto,etal.Slow wave sleep-inducing effects of first generation H1-antagonists[J].Biol.Pharm.Bull.1999,22(6):1079 -1082.
[85]Imeri L,Mancia M,Opp M.R.Blockade of 5-hydroxytryptamine(serotonin)-2 receptors alters interleukin-1-induced changes in rat sleep[J].Neuroscience. 1999,92(5):745-749.
[2]张宏,杜桂林,李显华,等.安眠颗粒治疗失眠的药效学研究.中药药理与临床.2003,19(2):42-43.
[3]顾晓路,梁茂新.安眠颗粒结构优化的步骤与方法.中国实验方剂学杂志.2008,14(6):22-26.
[4]游国雄,竺士秀,张可经.失眠与睡眠障碍疾病.北京:人民卫生出版社,2000:31.
[5]库宝善.改善睡眠药物开发新构想.生理科学进展.1992,23(2):107.
[6]张登本.中医神经精神病学[M].北京:中国医药科技出版社,2000:162-174.
[7]方药中,邓铁涛,李克光,等.实用中医内科学[M].上海:上海科学技术出版社,1989:345-349.
[8]高东艮.中医对睡眠与失眠的认识[J].中国中医基础医学杂志.1997,3:14-15.
[9]游国雄,竺士秀,张可经.失眠与睡眠障碍疾病[M] .北京:人民军医出版社.2000:1-5.
[10]刘平,兰胜作.失眠症临床检查与最佳治疗方案[M].天津:天津科学技术出版社,2002:14-17.
[11]罗和古.失眠[M].北京:中国医药科技出版社,2005:4-10.
[12]伍国锋,张文渊.脑电波产生的神经生理机制.临床脑电学杂志.2000,9(3) :188-190.
[13]佩雷兹·拉维.脑电波·睡眠之谜——一个魔幻的世界.上海:上海科学技术出版社,2001:12-13.
[14]赵忠新.临床睡眠障碍学[M].上海:第二军医大学出版社,2003:1-4.
[15]齐凤琴.具有改善睡眠作用药物的药效评价方法的建立:(硕士学位论文).哈尔滨:黑龙江中医药大学,2005.
[16]JOHN R.HUGHES.临床实用脑电图学[M].北京:人民卫生出版社,1999:51-58.
[17]张杰,王明时.睡眠脑电的研究[J].国外医学生物医学工程分册.1997,20(2):65-68.
[18]库宝善.慢波睡眠的药理学研究.北京医科大学学报.1999,31(3):204-208.
[19]李仪奎.中药药理实验方法学(第二版).上海:上海科学技术出版社,2006:217-227.
[20]徐叔云,卞如濂,陈修.药理实验方法学(第三版).北京:人民卫生出版社,2002:802-804.
[21]陈奇.中药药理研究方法学.北京:人民卫生出版社,1993:660-672.
[22]方文贤.中药药理研究实验设计浅析.中国中药杂志.1996,121(6):361-363.
[23] H.G.沃格尔,W.H.沃格尔.催眠作用药理学实验指南--新药发现和药理学评价.北京:科学技术出版社,2001:356.
[24]李树新,李中华,库宝善.家兔睡眠时相分析方法的建立.中国药理学通报.1996,12(5):429-430.
[25]靳照宇,库宝善,姚海燕,等.一种新的大鼠睡眠自动分析系统.中国药理学通报.1999,15(5):411-414.
[26]王绪平.苦参的镇静催眠作用研究:(硕士学位论文).杭州:浙江大学,2004.
[27]丁虹,乔文建.单胺类神经递质测定方法的研究.化学传感器.1992,12(2):14-19.
[28]匡培根.神经系统疾病药物治疗学[M].北京:人民卫生出版社,2002:1002.
[29]赵忠新,张红菊,黄流清.失眠的治疗药物及其使用方法研究进展.中国新药与临床杂志.2007,26(ll):851-856.
[30]靳元慧,曹玉凤,王金荣,等.浅谈失眠及镇静催眠药.中国执业药师.2006,(9):37-38.
[31]王泽民,王建女.睡眠障碍治疗药物的应用状况与评价[J] .医药导报.2005,(3):238.
[32]台大力,胡文祥,潭生建,等.催眠药研究进展[J].中国临床药学杂志.1998,7(4):195-197.
[33]刘郁.催眠镇静类药物的不良反应[J].辽宁医学杂志.2001,15(6):282-284.
[34] Wagner J,Wagner ML,Hening WA.Beyond benzo2 diazepines:alter native Pharmacologic agents for the treatment of insomnia[J].AnnPharm acother.1998,32(6):680-691.
[35] Maczaj M.Pharmacological treatment of insomnia[J].Drugs.1993,45(1):44-55.
[36]耿群美,李兰城,贾小英.苦参碱氧化苦参碱对小鼠脑中r-氨基丁酸和甘氨酸含量的影响[J].内蒙古医学杂志.1993,13(1):3.
[37]石京山,黄彬,吴芹,等.钩藤碱对小鼠活动和大鼠脑内的5-羟色胺及多巴胺影响[J].中国药理学报.1993,14(2):114.
[38]刘国卿,袁惠南,谢林,等.槐果碱等苦豆子生物碱对大鼠单胺代谢及多巴胺和5-羟色胺受体作用[J].药学学报.1987,(22):645.
[39]余建强,蒋袁絮,彭建中.氧化槐定碱对小鼠神经系统的影响[J].广东医学.2001,22(8):577.
[40]陈先瑜.秦艽生物碱药理作用(Ⅳ)对中枢神经系统作用[J].中药药理与临床.1992,8(5):45.
[41]马志清,刘国卿,霍小萍,等.左旋千金藤碱的中枢抑制作用[J].中国药科大学学报.1990,21(2):107.
[42]彭建中,金丽容,陈先瑜,等.脑室注射山莨菪碱、阿托品、樟柳碱和东莨菪碱的中枢作用[J].中国药理学报.1983,4(2):81.
[43]陈淑清,陈淑杰,刘健,等.不同产地黄连的体外抑菌活性与镇静作用[J].华西药学杂志.1990,5(3):168.
[44]周远鹏,江京莉.附子的研究(VI)附子中乌头碱及有关化合物的药理作用[J].中药药理与临床.1992,8(5):45.
[45]季宇彬,王月兰,台宝山,等.问荆碱对大鼠脑囊泡膜Mg2+-ATPase、Ca2+-ATPase抑制作用的动力学研究[J].中国中药杂志.1996,21(1):42.
[46]裴印权,岳微,崔景荣,等.胡椒碱衍生物的中枢药理作用研究[J].药学学报.1980,15(4):198.
[47]戴淑芳,高广猷.乌苏里藜芦碱对中枢神经系统的抑制作用[J].大连医科大学学报.1997,19(1):11.
[48]Rinura.Y. Studies on Scutellariae Radix[J].ChemPharm Bull.1981,29(8):2308.
[49]崔志清,王国祥,王立斌,等.雪莲黄酮甙A1对小鼠中枢神经系统作用[J].中草药.1995,26(5):247.
[50]高基铭,袁秉祥,李生正,等.淫羊藿总黄酮对家兔血小板功能及小鼠镇静、催眠及耐力作用的影响[J].西北药学杂志.1992,7(3):15.
[51]郭胜民,范晓霞,何建伟.酸枣仁总黄酮的中枢抑制作用[J].中药材.1998,21(11):578.
[52]汤臣康.五味子的化学和药理研究新进展[J].西北药学杂志.1994,9(6):279.
[53]连其琛,胡晓,上官珠,等.蛇床子素镇静作用的研究[J].中药新药与临床药理.2000,11(4):244.
[54]姜秀莲,曲淑岩,王一华,等.瑞香素对CNS的抑制作用[J].中药通报.1986,11(3):封2.
[55]顾健,胡锦官.石菖蒲及有效成分对中枢神经系统作用的实验研究[J].中药药理与临床.1999,15(3):19.
[56]张安平,陈敏珠,徐淑云.白芍总甙对大白鼠睡眠节律的影响[J].中药药理学通报. 1993,9(6):454.
[57]Honda.G.Isolation of Sedative Principles From Perilla Fruteslens[J].Chem Pharm Bull.1986,34(4):1672.
[58]郝洪谦,孙兵,郑开俊,等.郁金二酮对家猫睡眠节律电活动的调制作用[J].中草药.1994,25(8):423.
[59]王晖,许亚铭,王宗锐.薄荷醇对戊巴比妥中枢抑制作用的影响[J].现代应用药学.1995,12(3):1.
[60]齐治,田珍,秦玉香,等.糙叶败酱挥发油镇静作用的研究[J].天然产物研究与开发.1989,1(1):82.
[61]马越美,齐治,崔景荣,等.异叶败酱挥发油镇静作用的研究[J].中西医结合杂志.1987,7(11):671.
[62]池田正树.生姜的药理研究[J].国外医学·中医中药分册.1981,(2):53.
[63]于澍仁,尤胜权.芹菜甲素与乙素的抗惊厥作用[J].药学学报.1984,(8):566.
[64]吴尚霖,袁秉祥,马志义.酸枣仁油长期使用对小鼠催眠作用的影响[J].西北药学杂志.2001,15(3):114.
[65]胡盛珊,王大元,邱萍,等.枳实有效成分的药理活性比较[J].中草药.1994,25(8):419.
[66]周慧秋,于滨,乔婉红,等.甲基丁香酚药理作用研究[J].中医药学报.2000,28(2):79.
[67]沈雅琴,陈光娟,马树德,等.藁本中性油的镇静、镇痛、解热和抗炎作用[J].中西医结合杂志.1987,7(12):738.
[68]铃木幸子.丹皮酚的中枢作用[J].国外医学·中医中药分册.1983,(5):54.
[69]原田正敏.桂皮的药理学的研究(第一版)Cinnamaldehyde.中枢作用[J].药学杂志.1972,92(2):135.
[70]卞如濂.荆芥油的药理研究[J].浙江医科大学学报.1981,10(5):219.
[71]张罗修,余方考,郑秋影,等.雷公藤红素抑制抗体形成及抗炎作用[J].药学学报.1990,25(8):573.
[72]郭胜民,范晓霞,宋少刚,等.酸枣仁总皂甙中枢抑制作用研究[J].西北药学杂志.1996,11(4):166.
[73]倪小虎,杨柳,吕育齐,等.人参根及茎叶皂甙对群养及隔离孤独饲育小鼠神经药理作用的研究[J].中草药.1999,30(3):193.
[74]冯冰虹,孟青,郭晓玲,等.绞股蓝皂甙SH-6对脑内单胺递质及代谢产物的影响[J].中药新药与临床药理.1998,9(2):87.
[75]孙兵,郝洪谦,郑开俊,等.柴胡皂甙对猫睡眠节律电活动调制的实验研究[J].中草药.1994,25(2):82.
[76]高广猷,李传勋.山麦冬总皂甙对中枢神经系统抑制作用[J].中药药理与临床.1990,6(1):35.
[77]邝荔香.九子参总皂甙药理研究[J].时珍国医国药.1999,10(7):492.
[78]高勃.木总皂甙的中枢抑制作用[J].第四军医大学学报.1988,9(l):55.
[79]田新英,董承统.促睡眠植物提取液调节大鼠觉醒-睡眠周期的研究[J].脑与神经疾病杂志.2003,01(l):36-38.
[80]Claude Gottesmann,The transition from slow-wave sleep to paradoxical sleep:evolving facts and concepts of the neurophysiological processes underlying the intermediate stage of sleep[J].Neuroscience and Biobehavioral Reviews.1996,20(3):367-387.
[81]Youssef Slisli,Renaudde Beaurepaire.Interleukin-βand calcitonin,but not corticotropin-releasing factor,alter sleep cycles when injected into the rat hypothalamic lateral paraventricular area[J]. Neuroscience Letters.1999,265(4): 29-32.
[82]Pierre Gauthier,Christian Arnaud,Gabriel Gandolfo,etal.Influence of GABAB receptor antagonist on the sleep-waking cycle in the rat[J].BrainResearch.1997, 773(10):8-14.
[83]M.Yoshimoto,H.Higuchi,M.Kamata,etal.The effects of benzodiazepine (triazolam),cyclpyrrolone (zopiclone) and imidazopyridine (zolpidem) hypnoticson the frequence of hippocampal theta activityand sleep structure in rats[J]. European Neuropsychopharmacology.1999,9(1):29-35.
[84]Koichi Saitou,Yoshio Kaneko,Yukio Sugimoto,etal.Slow wave sleep-inducing effects of first generation H1-antagonists[J].Biol.Pharm.Bull.1999,22(6):1079 -1082.
[85]Imeri L,Mancia M,Opp M.R.Blockade of 5-hydroxytryptamine(serotonin)-2 receptors alters interleukin-1-induced changes in rat sleep[J].Neuroscience. 1999,92(5):745-749.