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Journal of Neurological Sciences (Turkish)
2012, Volume 29, Number 2, Page(s) 229-231
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Sodium Valproate and Sodium Dimercaptopropane Sulfonate, No Binding To Tetramine and No Reduction of Blood Tetramine Level
Viroj WIWANITKIT
Wiwanitkit House, Bangkhae, Bangkok Thailand
Summary
Tetramine is considered as a highly poisonous substance that can cause the neurological disorder to anyone who intake it within a few minutes. The clonic tonic seizure can be developed and death can be the finalized result. Here, the author assesses whether the two presently used antidotes have any possibility to reduce the tetramine level in blood level. The author tries to us e a molecular docking technique to study the mechanism of sodium valproate and sodium dimercaptopropane on tetramine. Of interest, there is no detected interaction. This confirms the fact that there is no direct neutralization effect. Hence, it can explain the fact that there is no significant reduction of blood tetramine level in intoxication case after getting the two antidotes.
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  • Summary
  • Introduction
  • Methods
  • Results
  • Discussion
  • References
    • Introduction
    Tetramine is a new focused emerging poison that is reported in epidemic pattern in China and other countries. The problem of tetramine contamination in food and milk becomes the public health threaten(3,5,9). Tetramine is considered as a highly poisonous substance that can cause the neurological disorder to anyone who intake it within a few minutes(9). The clonic tonic seizure can be developed and death can be the finalized result(9).

    To treatment, there are many reports on several therapeutic options for acute tetramine poisoning(3,5,9). Sodium valproate and sodium dimercaptopropane sulfonate are the two widely mentioned antidotes(2). However, it was recently noted that these two drugs did not effectively reduce the tetramine level(7) in blood but control symptoms(1,4,11-13). Here, the author tries to us e a molecular docking technique to study the mechanism of sodium valproate and sodium dimercaptopropane on tetramine.
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  • Summary
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
    • Methods
    This work was based on a theoretical bioinformatics analysis. To test the possible reaction between tetramine and two studied antidotes, a standard molecular docking technique using tool namely PatchDock(6) was done. The aim is to assess whether there is any predicted resulted complex. This technique is a standard technique for assessment the possible reaction between two studied molecules in reference database (Chemical Infobox, available online at http://en.wikipedia.org/wiki/Wikipedia:CHEMBOX)(10). This approach is already for reliability in previously published paper(10).
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  • Summary
  • Introduction
  • Methods
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  • Disscussion
  • References
    • Results
    According to the bioinformatics analysis, it appears that there is no predicted result complex between “tetramine” and “sodium valproate” and between “tetramine” and “sodium dimercaptopropane sulfonate.”
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  • Summary
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
    • Discussion
    The problem of tainted milk from China due to melamine is the recent hot issue in public health. However, there are also other problematic contaminations. The tetramine contaminated milk and food is another interesting problem. Unlike melamine, the main toxic manifestation of acute tetramine intoxication is neurological disorder. Status epilepticus can be seen after a few minutes of exposure(3,5,9).

    The treatment of acute tetramine intoxication is interesting. Fatality in affected cases is confirmed and this brings attention medical society to find for the best alternative therapeutic choice(1,2,4,7,11-13). Here, the author assesses whether the two presently used antidotes have any possibility to reduce the tetramine level in blood level. In case that the reduction ability is possible, there must be a direct binding interaction, as a neutralization process, between antidote and tetramine molecule. This can be traced based on advanced bioinformatics technology.

    In this work, the author uses a standard molecular docking technique to test the interaction. Of interest, there is no detected interaction. This confirms the fact that there is no direct neutralization effect. Indeed, the indirect antidotal effect via receptor in brain is mentioned for the two studied antidotes(1–2,7). Hence, it can explain the fact that there is no significant reduction of blood tetramine level in intoxication case after getting the two antidotes(7). The direct removal of the tetramine before absorption, as gastric lavage(8) or hemoperfusion therapy(7) seems to be more appropriate in reduction or diluting the level of tetramine in blood stream.

    Received by: 18 September 2009
    Revised by: 13 December 2011
    Accepted: 07 March 2012
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  • Summary
  • Introduction
  • Methods
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  • Discussion
  • References
    • References

    1) Bai H, Zhang SL, Zhang HS, Ji JT, Ma PB, Wang HS, Bai YW, Zhou XR, Ding MB, Lu XR, Sun CY. Evaluation of therapeutic project on acute tetramethylene disulphotetramine poisoning and effect on intelligence in children. Zhonghua Yu Fang Yi Xue Za Zhi. 2005 Mar;39(2):95-8.

    2) Chan CK, Chan YC. Antidotes for tetramine poisoning. Hong Kong Med J. 2006 Feb;12(1):87.

    3) Chau CM, Leung AK, Tan IK. Tetramine poisoning. Hong Kong Med J. 2005 Dec;11(6):511-4.

    4) Ji JT, Tian XQ. Infantile tetramine poisoning treated with sodium dimercaptosulfonate: clinical analysis of 54 cases. Zhonghua Er Ke Za Zhi. 2003 Dec;41(12):948-9.

    5) Lu Y, Wang X, Yan Y, Xiao Z, Stephani U. Nongenetic cause of epileptic seizures in 2 otherwise healthy Chinese families: tetramine--case presentation and literature survey. Clin Neuropharmacol. 2008 Jan-Feb;31(1):57-61.

    6) Schneidman-Duhovny D, Inbar Y, Polak V, Shatsky M, Halperin I, Benyamini H, Barzilai A, Dror O, Haspel N, Nussinov R, Wolfson HJ. Taking geometry to its edge: fast unbound rigid (and hinge-bent) docking. Proteins 2003; 52: 107-12.

    7) Sun P, Han J, Weng Y. The antidotal effects of high-dosage gamma-aminobutyric acid on acute tetramine poisoning as compared with sodium dimercaptopropane sulfonate. J Huazhong Univ Sci Technolog Med Sci. 2007 Aug;27(4):419-21.

    8) Wang LH, Xian MP, Geng WQ, Qin ZL, Li YX. Logistic regression analysis of factors influencing clinical therapeutic effect on acute tetramine poisoning. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2004 Feb;22(1):26-8.

    9) Whitlow KS, Belson M, Barrueto F, Nelson L, Henderson AK. Tetramethylenedisulfotetramine: old agent and new terror. Ann Emerg Med. 2005 Jun;45(6):609-13.

    10) Wiwanitkit V. Molecular structure of BRCA1-estrogen receptor alpha-estrogen complex: relevance to breast cancer? Asian Pac J Cancer Prev. 2005 Oct-Dec;6(4):561-2.

    11) Zhang HS, Zhou J, Zhang SL, Wu YQ, Sun CY. Toxicokinetics of tetramethylene disulphotetrane. Zhonghua Yu Fang Yi Xue Za Zhi. 2005 Mar;39(2):91-4.

    12) Zhang CY, Zhu TJ, Hu GX, Chen XY, Liu DX, Chen ZK. Effect of sodium dimercaptopropanesulfonate on antagonism of tetramethylenedisulphotetramine to GABA receptor. Acta Pharmacol Sin. 2001 May;22(5):435-9.

    13) Zhao CH, Lu ZQ, Li HP, Li JR. Treatment with diazepanum and dimercaptopropansulfonate sodium for acute tetramine intoxication. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2004 Feb;22(1):68-9.
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  • Summary
  • Introduction
  • Methods
  • Results
  • Discussion
  • References
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