Experimental studies on the anticonvulsion effect and mechanism of Samulanshintang

사물안신탕(四物安神湯)의 항경련(抗經攣) 효과(效果) 및 작용기전(作用機轉)에 관(關)한 실험적(實驗的) 연구(硏究)

  • Kwon Bo-Hyung (Dept. of Oriental Neuropsychiatry, College of Oriental Medicine, Woo Suk University) ;
  • Gu Byung-Su (Dept. of Oriental Neuropsychiatry, College of Oriental Medicine, Dong Guk University)
  • 권보형 (우석대학교 한의과대학 신경정신과학교실) ;
  • 구병수 (동국대학교 한의과대학 신경정신과학교실)
  • Published : 1999.12.30

Abstract

For experimental studies on the anticonvulsion effect and it was measured in mice that toxigenic effect, influence on the central nervous system, anticonvulsion effect, mechanism of anticonvulsion effect by change of GABA level and glutamic acid in brain, effect of the creation and degradation system of brain oxygen free radicals in convulsion. The results were obtained as follows: 1. Samulanshintang was perfect medicine without toxigenic effect. 2. Pretreatment of Samulanshintang did not influence on the central nervous system. 3. Pretreatment of Samulanshintang did not influence on maximal electric seizure(MES), strychnine, bicuculine and picrotoxin, but pentylenetrazol(PTZ)-induced convulsion significantly decreased. 4. Effect of Samulanshintang except for Jinsa on the PTZ-Induced convulsion decreased. 5. Effect of Samulanshintang fragrance(SMATF) and Samulanshintang distiled water(SMATW) on the PTZ-induced convulsion did not influence. 6. Decrease of brain GABA level in PTZ-induced convulsion was increased by pretreatment of Samulanshintang. 7. Decrease of brain glutathione content in PTZ-induced convulsion was increased by pretreatment of Samu- lanshintang. 8. GABA-T activity increased by PTZ-induced was controlled by the pretreatment of Samulanshintang. 9. Increase of brain lipid peroxide content in PTZ-induced convulsion was decreased by pretreatment of Samulanshintang. 10. Significant increase of brain xanthine oxidase and aldehyde oxidase activities in PTZ-induced was controlled by pretreatment of Samulanshintang. 11. Decrease of brain superoxide dismutase(SOD), catalase and glutathione peroxidase activities in PTZ-induced was decreased by pretreatment of Samulanshintang. From the above results, Samulanshintang was perfect medicine without toxigenic effect and was recognized anticonvulsion effect by decreasing brain glutamic acid level and increasing brain GABA level. Samulanshintang have an effect on creation and degradation system of brain oxygen free radicals in convulsion, thus it was considered that Samulanshintang could be applied in convulsive disorder as epilepsy, febrile seizure and spasm etc.

Keywords

References

  1. 최신정신의학 민성길(외)
  2. 精神醫學 李定均
  3. 신경과학 아담스신경과학 편찬위원회(편)
  4. 精神醫學辭典 李丙允
  5. 病과 治療 李文鎬(외)
  6. Selected writings of John Huhglings Jackson v.1 On the anatomical, physiological and pathological initigation of epilepsies. Jackson, J.H.;Jackson, J.H.(eds.)
  7. 傷寒論精解 文濬典(외)
  8. 東醫小兒科學 丁奎萬
  9. 諸病源候論校釋 南京中醫學院
  10. 中醫內科辨證學 王顯明
  11. 實用中醫內科學 黃文東
  12. 類證治裁 林범琴
  13. 醫學入門 李천
  14. 證治準繩 王肯堂
  15. 證治彙補 李用碎
  16. 外臺秘要(上) 王燾
  17. 儒門事親提要 張子和
  18. 吳批醫學心悟 程國彭
  19. 本草綱目 李時珍
  20. 濟衆新編 康命吉
  21. 三因方 陳言
  22. 備急千金要方 遜思邈
  23. 古今醫鑑 龔信
  24. 素問玄機原病式解釋 람永升
  25. 신경학원론 서울대학교의과대학
  26. Neurol. v.15 Neurological sequelae following dilantin overdose in a patient and in experimental animals. Kokenge, R.;Kutt, H.;McDowell, F.
  27. J. Pharmacol. Exp. Ther. v.186 A comparison of the anticonvulsnat, neurotoxic lethal effects of diphenylbarbituric acid, phenobarbital, diphenylhydantoin in the mouse. Raines, A.;Niner, J.M.;Pace, D.G.
  28. Biochem. Pharmacol. v.12 the effect upon mice if intraventricular injection of excitant and depressant amino acids. Crawford, J.M.
  29. Nature v.287 Aspartate and glutamate as possible neurotransmitters of cells in layer 6 of the visual cortex. Baughman, R.W.;Gilbert, C.D.
  30. Science v.216 Anticonvulsant action of antagonists of neuronal excitation due to dicarboxylic amino acids. Croucher, M.J.;Collins, J.F.;Meldrum, B.S.
  31. Adv. Neurol. v.19 Epidermiology of epilepsy. Hause, W.A.
  32. Cleve. Clin. Q. v.51 Antiepileptic drug development program. Porter, R.J.
  33. 東醫精神醫學 黃義完(외)
  34. 精校黃帝內經靈樞 洪元植
  35. 精校黃帝內經素問 洪元植
  36. 金匱要略 張機
  37. 增補萬病回春 龔廷賢
  38. 東醫寶鑑 許浚
  39. 東醫精神科學 柳熙英
  40. 경희한의대논문집 v.6 四物安神湯의 效能에 關한 實驗的 硏究 黃義完(외)
  41. 동의신경정신과학회지 v.4 no.1 歸脾湯 및 四物安神湯의 臨床效果에 關한 硏究 柳敞烈(외)
  42. 동의신경정신과학회지 v.5 no.1 拘束스트레스 흰쥐에 미치는 四物安神湯의 效能에 關한 硏究 權保亨(외)
  43. Psychopharmacologia, (Berl.) v.14 An investigation of a new instrument to measure motor activity of samll animals. Svensson, T.H.;Thieme, G.
  44. J. Am. Pharm. Assoc. v.46 Pharmacological activity of a series of basic esters mono and dialkyl malonic acid. Dunham, N.W.;Miya, T.S.;Edwards, C.D.
  45. Arch. Int. Pharmacodyn. v.92 Design and use of a new electoshock seizure apparatus, and analysis of factors altering seizure threshold and pattern. Woodbury, L.A.;Davenport, V.D.
  46. Jap. J. Pharmacol. v.22 Changes in sensitivity ot convulsion in mice with olfactory bulb ablation. Araki, S.;Ueki, S.
  47. Arch. Int. Phamacodyn. v.188 Anticonvulsant properties of diphenylthiohydantoin. Shon, Y.J.;Levitt, B.;Raines, A.
  48. Epilepsia v.33 Relative anticonvulsant effect of GABAmimetic and GABA modulatory agents. Holland, K.D.;McKeon, A.C.;Canney, D.J.;Covey, D.F.;Ferrendelli, J.A.
  49. J. Chromatography v.336 Reversed~phase high performnace liquid chromatographic method for determination of brain glutamate decarboxylase suitable for use in kinetic studies. Allen, I.C.;Griffthis, R.
  50. Anal. Biochem. v.95 Assay for lipid peroxides in animal tissue by thiobarbituric acid reaction. Ohkawa, H.;Ohishi, N.;Yaki, Y.
  51. Arch. Biophys. v.30 Tissue sulfhydryl group. Ellman, G.L.
  52. Method of enzymatic analysis v.2 Bergmeyer, H.U.
  53. J. Biol. Chem. v.244 The regulation of rat liver xanthine oxidase : Conversion in vitro of the enzyme activity from dehydrogenase(Type D) to oxidase(Type O) Stirpe, F.;Della, C.E.
  54. J Biol. Chem. v.237 Hepatic aldehyde oxidase : Purification and properties Rajagopalan, K.V.;Fridovich, I.;Handler, P.
  55. Eur. J. Biochem. v.47 Involvement of the superoxide anion radical in the autooxidation of pyrogallol and a convenient assay for superoxide dismutase Marklund, S.;Marklund, G.
  56. Methods of enzymetic analysis Catalase Aebi, H.;Vergmeyer, M.U.
  57. J. Lab. Clin, Med. v.70 Studies on the quantitative and qualitative charaterization of erythrocytes glutathione peroxidase Paglia, E.D.;Valentine, W.N.
  58. 藥物學 및 毒性學實驗 주왕기(외)
  59. J. Biol. Chem. v.193 Protein measurment with the folin phenol reagent. Lowry, O.H.;Rodebrough, N.J.;Farr, A.L.;Randali, R.J.
  60. 中醫腦病證治 呂光榮(외)
  61. 中國傳統精神病理學 何裕民
  62. 心-腦-神志病辨證論治 張明淮(외)
  63. 韓藥臨床應用 李尙仁(외)
  64. 申氏本草學 申佶求
  65. 中醫臨床大全 楊思澍(외)
  66. 小兒藥證直訣 錢乙
  67. 神經精神醫學 v.23 no.3 癎疾重疊患者의 臨床分析 張필립
  68. 中醫兒科學 上海中醫學院(편)
  69. 金匱要略註解 李載熙
  70. 內科學 李文鎬(외)
  71. 應急處置 醫學敎育硏修院(편)
  72. 大韓醫學協會誌 v.25 no.5 重金石 中毒 金明宰
  73. 大韓神經外科學會誌 v.3 no.2 成人 痙攣의 原因的 考察 서정규(외)
  74. Arch. Neurol. Psychiatr. v.39 Cerebral dysrhythmias of epilepsy. Gibbs, E.L.;Gibbs, F.A.;Lennox, W.G.
  75. Epilepsy and related disorders. Lennox, W.G.
  76. Review of Physiology, pharmacology and Biochemistry v.69 amino acid transmitters in the mammalian nervous system. Curtis, D.R.;Johnston, G.A.R.
  77. Brain. Res. Bull. v.5 Mucimol: Brain pernatration and anticonvulsant potency following GABA-T inhibition. Enna, S.J.;Maggi, A.;Worms, P.;Lloyd, K.G.
  78. 臨床病理화일 이귀녕(외)
  79. J. Neurochem. v.7 Amino acid and protein metabolism. VI. Cerebral compartments of glutamic acid metabolism. Berl, S.;Lajtha, A.;Waelsch, H.
  80. Neurol. v.15 Neurological sequelae following Dilantin overdose in a patient and in experimental animals. Kokenge, R.;Kutt, H.;McDowell, F.
  81. J. Pharmacol. Exp. Ther. v.186 A comparison of the anticonvulsant, neurotoxic and lethal effects of diphenylbarbituric acid, phenobarbital, diphenylhydantoin in the mouse. Raines, A.;Niner, J.M.;Pace, D.G.
  82. Epilepsia v.21 Hepatotoxicity of sodium valproate and other anticonvulsant in rat hepatocyte cultures. Kinsley, E.;Tweedale, R.;Tolman, K.G.
  83. Antiepileptic drugs Trimethadione toxicity. Booker, H.E.;Woodbury, D.M.;Penry, J.U.;Pippenger, C.E.(eds.)
  84. 경희한의대논문집 v.4 小兒熱性疾患에 應用되는 瀉靑丸이 鎭痛, 鎭痙, 解熱作用에 미치는 影響 李源哲(외)
  85. 경희한의대논문집 v.5 芍藥甘草湯이 抗痙攣, 鎭痛, 解熱, 抗炎症 및 抗潰瘍 效果에 미치는 影響 丁奎萬(외)
  86. 대한한의학회지 v.14 no.1 加味鉤藤飮의 抗痙攣作用에 關한 實驗的 硏究 金德坤(외)
  87. 경희한의대논문집 v.8 小靑龍湯의 鎭痛, 抗痙攣 및 흰쥐의 肺損傷에 미치는 影響 金基昌(외)
  88. 동의신경정신과학회지 v.8 no.1 淸心溫膽湯이 白鼠의 抗痙攣, 解熱, 鎭痛, 鎭靜 및 GABAergic system에 미치는 影響 金在亨(외)
  89. 동의신경정신과학회지 v.5 no.1 抑肝散과 抑肝散加味方의 鎭痙 및 鎭痛效果에 關한 實驗的 硏究 玄禹天(외)
  90. 대한한의학회지 v.9 no.2 蔓荊子散의 鎭痛, 解熱, 鎭靜 및 消炎效果에 미치는 影響 張炳秀(외)
  91. Arch. Exp. pathol. Pharmakol. v.116 Pentametylenetetrazole(Cordiazol) Hildebrandt, F.
  92. Epilepsia v.10 Laboratory evaluation of antiepileptic durgs. Swinyard, E.A.
  93. Electroencephalogr. Clin. Neurophysiol. v.14 Intravenous, cortical and intraventricular dose~effect relationship of pentylenetetrazol, picrotoxin and deslanoside in dogs. Bitcher, R.P.;Kanai, T.;Wang, S.C.
  94. Neurochem. Res. v.7 Acute effect of sodium valproate and $\gamma$~vinyl GABA on regional amino acid metabolism in the rat brain. Chapman, A.G.;Riley, K.;Evans, M.G.;Meldrum, B.S.
  95. Nature v.284 A site for the potentiation of GABA~mdeiated responses by benzokiazepins. Simonds, M.A.
  96. Trends Pharmacol. Sci. v.3 Baclofen; 10 years on. Bowery, N.G.
  97. Molecular Neurobiology of the Mammalian Brain Inhibitory amino acid neurotransmitters Mc-Geer, P.L.;Eccles, S.J.C.;Mc-Geer, E.G.;Mc~Geer, P.L.(et al.)
  98. Trends Pharmacol. Sci. v.10 Multiplicity of GABAA-benzodiazepine receptors. Sieghart, W.
  99. Trends Pharmacol. Sci. v.10 GABAB receptors and their significance in mammalian pharmacology. Bowery, N.G.
  100. Biochem. Pharmacol. v.28 Inhibitors of GABA metabolism Metcalf, B.W.
  101. J. Chromatography v.277 Chromatographic analysis of glutamic acid decarboxylase in biological samples. Holdiness, M.R.
  102. Epilepsia v.20 Remission of seizures and relapse in patients with epilepsy. Annegers, J.F.;Hauser, W.A.;Elveback, L.R.
  103. Epilepsia v.25 Open trials with vaproate in epilepsy. Dulac, O.;Arthuis, M.
  104. NEJM v.311 The prognosis for seizure control in newly diagnosed epilepsy. Elwes, R.D.C.;Johnson, A.L.;Shorvon, S.D.;Reynolds, E.H.
  105. Epilepsia v.29 Adjunctive therapy in resistant epilepsy. Callaghan, N.;Goggin, T.
  106. J. Child Neuro. v.6 Vigavatrin in childhood epilepsy. Dulac, O.;Chiron, C.;Luna, D.
  107. Ann. Neurol. v.32 Felbamate monotherapy: controlled trial in patients with partial onset seizure. Sachdeo, R.;Kramer, L.D.;Rosenberg, A.;Sachdeo, S.
  108. Epilepsy Res. v.14 Efficancy and safety of zonisemide: results of a mulicenter study. Leppik, I.E.;Willmore, L.J.;Homan, R.W.
  109. B.M.J. v.302 Medical assessment and treatment of chronic epilepsy. Shorvon, S.D.
  110. J. Med. Chem. v.34 Preparation and anticonvulsant activity of a series of functionalized $\alpha$-heteroatom-substituted amino acids. Harold, K.;Kailash, N.S.;Phillippe, L.;David, W.R.;J. David, L.
  111. J. Pharmaceut. Sci. v.83 Substituted 2-bezothiazolamines as sodium flux inhibitors: quantitative structure-activity relationships and anticonvulsion activity. Sheryl, J.H.;Michael, J.R.;Daniel, F.O.;Graham, J.;Roy, D.S.;Denise, K.B.;Laura, F.C.;Mark, G.V.;Peter, A.B.
  112. J. Am. Pharm. Assoc. v.46 Pharmacological activity of a series of bacis esters mono- and dialkyl malonic acid. Dunham, N.W.;Miya, T.S.;Edwards, C.D.
  113. J. Pharmacol. Exp. Ther. v.187 Role of detoxifying enzymes in bromobenzene- induced liver necrosis. Zampaglione, N.;Jollow, D.J.;Mitohell, J.R.;Manrick, M.;Gillette, J.R.
  114. Nature. v.22 Specific and ireversible inhibition of lysozyme by 2, 3, -epoxypropyl $\beta$-glycosides of N-acetyl O-glucosamine olimers. Thomas, W.E.;Mekeluy, J.F.;Shorn, N.
  115. Drug. Exp. Clin. Res. v.8 Epoxypeptides, A novel group to metabolic inhibitrs in prokariotic and eukariotic micro-organisms. Milewski, E.
  116. Biochem. Pharmacol. v.31 Reactive metabolism and caroiogenicity of halogenated ethylenes. Bolt, H.M.;Laib, R.J.;Filser, J.G.
  117. Epilepsia v.21 Hepatotoxicity of sodium valproate and other anticonvulsants in rat hepatocyte culture. Kinsley, E.;Tweedale, R.;Tolman, K.G.
  118. Antiepileptic drugs Trimethadione toxicity. Booker, H.E.;Woodbury, D.M.;Penry, J.U.;Pippenger, C.E.(eds.)
  119. Epilepsia v.4 Anticonvulsant activity and toxicity of phesuximade, methsuximide and ethosuximide. Chen, G.;Weston, J.K.;Bratton, A.C.
  120. Revista Espanola de Fisiologia v.39 Method of assay for 4-aminobutyrate-2- oxoglutarate aminotransferase. Gonzalez, M.P.;Canadas, S.;Munoz, F.;Sanchez-Pieto, J.;Morales, V.
  121. Pharmazie. v.49 Einfluss von propranolol auf die lipid peroxidation im cortex pentetrazol-gekindelter ratten. Scheibler, P.;Kittner, H.
  122. J. Biol. Chem. v.244 Digestive activity of lysosome. III. The digestion of lipids by extracts of rat liver lysosome Fowler, S.;De Duve, C.
  123. Medicine(Baltimore) v.78 Pancrestitis and hyperlipemia : a study of serum lipid alteration in 25 patients with acute pancreatitis Greenberg, N.J.;Hatch, F.T.;Drummey, G.D.;Isselbacher, K.J.
  124. J. Clin. Invest v.62 Metabolic control of circulation. Liang, C.S.;Lowenstein, J.M.
  125. J. Submicrose. Cytol. v.12 Contractility of myofibroblasts during experimental liver cirrhosis Irle, C.;Cocher, O.;Gabbiani, G.
  126. Lancet v.2 Could you superoxide cause cirrhosis? Lewis, K.O.;Paton, A.
  127. biochem. J. v.126 Xanthine oxidase type(D) in the intestinal and other organs of the rat. Battelli, M.G.;Della, Corte, E.;Stripe, F.
  128. 프리라디칼 金永坤(외)
  129. J. Parasit. v.55 Liver xanthine oxidase activity in mice infected with schistosoma mansoni. Crosby, P.F.;Matos, M.L.;Rivera-Collazo, E.
  130. Infec. Immun. v.3 Induction of xanthine oxidase by virus infection in new born mice. Ziegler, D.W.;Hutchinson, H.D.;Kissling, R.E.
  131. J. Biol. Chem. v.216 Purification of liver xanthine oxidase. Kielley, R.K.
  132. J. Lab. Clin. Med. v.74 A sensitive and nonradioactive assay from serum and tissue xanthine oxidase. Ramboer, R.W.H.
  133. J. Biol. Chem. v.243 The reduction of cytochrome C by milk xanthine oxidase. McCord, J.M.;Fridovich, I.
  134. Biochem. J. v.131 Characterization of alternative molecular forms of xanthine oxidase in the mouse. Duke, E.J.;Joyce, P.;Ryan, J.P.
  135. Biochem. Biophys. Res. Commun. v.141 no.3 Absence xanthine oxidase and xanthine dehydrogenase in the rabbit anyocardium. Grum, C.M.;Ragsdale, R.A.;Ketai. L.H.;Shlater, M.
  136. Biochim. Biophys. Res. Commun. v.143 no.2 Impurities in commercial xanthine oxidase inhibit Ca-pump and interfere in contractility of pig coronary artery. Grover, A.K.;Samson, S.E.
  137. Oxygen radicals and Parkinson's disease, Oxygen radicals and tissue injury Cohen, G.
  138. Xenobiotica v.20 Cytochrome P450-dependent formation of oxygen radicals. Isoenzyme-specific inhibition of P450-mediated reduction of oxygen and carbon tetrachloride Persson, J.O.;Terelius, Y.;Ingelman-Sundberg, M.