Biomolecules & Therapeutics

  • 제17권2호
  • /
  • Pages.168-174
  • /
  • 2009
  • /
  • 1976-9148(pISSN)
  • /
  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
권호 표지
DOI QR코드

DOI QR Code

Evaluation of Immunological Safety of Topiramate, an Anti-epileptic Drug, in a Murine Model

  • 발행 : 2009.04.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Epilepsy is one of the most common neurological disorders, and topiramate (TPM) is one of the most effective drugs that can render patients seizure-free. The focus of the present study was to evaluate the immunological safety of TPM in a mouse model. We examined the in vitro effect of TPM on immune functions of BV2 microglial cells, RAW 264.7 macrophages, B cells, T cells, and dendritic cells. We also examined the in vivo effect of TPM on mouse immune organs, such as lymph node, spleen, and thymus. When cells were directly treated with TPM at concentrations from 1 to $30{\mu}g/ml$, TPM did not affect nitrite production by BV2 cells and macrophages, proliferation of B cells and T cells, or maturation of dendritic cells. In addition, TPM did not change the weight and cellularity of lymph nodes, spleen, and thymus in vivo at doses from 3 to 100 mg/kg injected i.p. into mice once a day for 4 consecutive days. These data showed that TPM, which is widely used as an anti-epileptic drug, is immunologically safe.

키워드

참고문헌

  1. Ben-Menachem, E. (1996). Expanding antiepileptic drug options: clinical efficacy of new therapeutic agents. Epilepsia 37 (Suppl 2), S4-S7 https://doi.org/10.1111/j.1528-1157.1996.tb06031.x
  2. Ben-Menachem, E. (2003). Levetiracetam: treatment in epilepsy. Expert Opin. Pharmacother. 4, 2079-2088 https://doi.org/10.1517/14656566.4.11.2079
  3. Ben-Menachem, E., Henriksen, O., Dam, M., Mikkelsen, M., Schmidt, D., Reid, S., Reife, R., Kramer, L., Pledger, G. and Karim, R. (1996). Double-blind, placebo-controlled trial of topiramate as add-on therapy in patients with refractory partial seizures. Epilepsia 37, 539-543 https://doi.org/10.1111/j.1528-1157.1996.tb00606.x
  4. Bootsma, H. P., Aldenkamp, A. P., Diepman, L., Hulsman, J., Lambrechts, D., Leenen, L., Majoie, M., Schellekens, A. and de Krom, M. (2006). The effect of antiepileptic drugs on cognition: patient perceived cognitive problems of topiramate versus levetiracetam in clinical practice. Epilepsia 47 (Suppl 2), 24-27 https://doi.org/10.1111/j.1528-1167.2006.00683.x
  5. Bootsma, H. P., Ricker, L., Diepman, L., Gehring, J., Hulsman, J., Lambrechts, D., Leenen, L., Majoie, M., Schellekens, A., de Krom, M. and Aldenkamp, A. P. (2007). Levetiracetam in clinical practice: long-term experience in patients with refractory epilepsy referred to a tertiary epilepsy center. Epilepsy Behav. 10, 296-303 https://doi.org/10.1016/j.yebeh.2006.11.016
  6. Bootsma, H. P., Ricker, L., Diepman, L., Gehring, J., Hulsman, J., Lambrechts, D., Leenen, L., Majoie, M., Schellekens, A., de Krom, M. and Aldenkamp, A. P. (2008a). Long-term effects of levetiracetam and topiramate in clinical practice: A head-to-head comparison. Seizure 17, 19-26 https://doi.org/10.1016/j.seizure.2007.05.019
  7. Bootsma, H. P., Vos, A. M., Hulsman, J., Lambrechts, D., Leenen, L., Majoie, M., Savelkoul, M., Schellekens, A. and Aldenkamp, A. P. (2008b). Lamotrigine in clinical practice: long-term experience in patients with refractory epilepsy referred to a tertiary epilepsy center. Epilepsy Behav. 12, 262-268 https://doi.org/10.1016/j.yebeh.2007.10.004
  8. Callaghan, B. C., Anand, K., Hesdorffer, D., Hauser, W. A. and French, J. A. (2007). Likelihood of seizure remission in an adult population with refractory epilepsy. Ann. Neurol. 62, 382-389 https://doi.org/10.1002/ana.21166
  9. Chung, S., Wang, N. and Hank, N. (2007). Comparative retention rates and long-term tolerability of new antiepileptic drugs. Seizure 16, 296-304 https://doi.org/10.1016/j.seizure.2007.01.004
  10. De Simoni, M. G., Perego, C., Ravizza, T., Moneta, D., Conti, M., Marchesi, F., De Luigi, A., Garattini, S. and Vezzani, A. (2000). Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. Eur. J. Neurosci. 12, 2623-2633 https://doi.org/10.1046/j.1460-9568.2000.00140.x
  11. DeLorenzo, R. J., Sombati, S. and Coulter, D. A. (2000). Effects of topiramate on sustained repetitive firing and spontaneous recurrent seizure discharges in cultured hippocampal neurons. Epilepsia 41(Suppl 1), S40-44 https://doi.org/10.1111/j.1528-1157.2000.tb06048.x
  12. Faught, E., Wilder, B. J., Ramsay, R. E., Reife, R. A., Kramer, L. D., Pledger, G. W. and Karim, R. M. (1996). Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 200-, 400-, and 600-mg daily dosages. Topiramate YD Study Group. Neurology 46, 1684-1690 https://doi.org/10.1212/WNL.46.6.1684
  13. Follett, P. L., Deng, W., Dai, W., Talos, D. M., Massillon, L. J., Rosenberg, P. A., Volpe, J. J. and Jensen, F. E. (2004). Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia: a protective role for topiramate. J. Neurosci. 24, 4412-4420 https://doi.org/10.1523/JNEUROSCI.0477-04.2004
  14. French, J. A., Kanner, A. M., Bautista, J., Abou-Khalil, B., Browne, T., Harden, C. L., Theodore, W. H., Bazil, C., Stern, J., Schachter, S. C., Bergen, D., Hirtz, D., Montouris, G. D., Nespeca, M., Gidal, B., Marks, W. J. Jr., Turk, W. R., Fischer, J. H., Bourgeois, B., Wilner, A., Faught, R. E. Jr., Sachdeo, R. C., Beydoun, A. and Glauser, T. A. (2004a) Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy: report of the therapeutics and technology assessment subcommittee and quality standards subcommittee of the american academy of neurology and the american epilepsy society. Neurology 62, 1252-1260 https://doi.org/10.1212/01.WNL.0000123693.82339.FC
  15. French, J. A., Kanner, A. M., Bautista, J., Abou-Khalil, B., Browne, T., Harden, C. L., Theodore, W. H., Bazil, C., Stern, J., Schachter, S. C., Bergen, D., Hirtz, D., Montouris, G. D., Nespeca, M., Gidal, B., Marks, W. J. Jr., Turk, W. R., Fischer, J. H., Bourgeois, B., Wilner, A., Faught, R. E. Jr., Sachdeo, R. C., Beydoun, A. and Glauser, T. A. (2004b). Efficacy and tolerability of the new antiepileptic drugs, I: Treatment of new-onset epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society. Epilepsia 45, 401-409 https://doi.org/10.1111/j.0013-9580.2004.06204.x
  16. Gibbs, J. W. 3rd, Sombati, S., DeLorenzo, R. J. and Coulter, D. A. (2000). Cellular actions of topiramate: blockade of kainate-evoked inward currents in cultured hippocampal neurons. Epilepsia 41(Suppl 1), S10-16 https://doi.org/10.1111/j.1528-1157.2000.tb02164.x
  17. Haghikia, A., Ladage, K., Hinkerohe, D., Vollmar, P., Heupel, K., Dermietzel, R. and Faustmann, P. M. (2008). Implications of antiinflammatory properties of the anticonvulsant drug levetiracetam in astrocytes. J. Neurosci. Res. 86, 1781-1788 https://doi.org/10.1002/jnr.21639
  18. Han, S. B., Kim, Y. H., Lee, C. W., Park, S. M., Lee, H. Y., Ahn, K. S., Kim, I. H. and Kim, H. M. (1998). Characteristic immunostimulation by angelan isolated from Angelica gigas Nakai. Immunopharmacology 40, 39-48 https://doi.org/10.1016/S0162-3109(98)00026-5
  19. Hanisch, U. K. (2002). Microglia as a source and target of cytokines. Glia 40, 140-155 https://doi.org/10.1002/glia.10161
  20. Jeon, Y. J., Han, S. B., Ahn, K. S. and Kim, H. M. (2000). Differential activation of murine macrophages by angelan and LPS. Immunopharmacology 49, 275-284 https://doi.org/10.1016/S0162-3109(00)00243-5
  21. Kim, H. M., Kang, J. S., Park, S. K., Lee, K., Kim, J. Y., Kim, Y. J., Hong, J. T., Kim, Y. and Han, S. B. (2008). Antidiabetic activity of angelan isolated from Angelica gigas Nakai. Arch. Pharm. Res. 31, 1489-1496 https://doi.org/10.1007/s12272-001-2135-9
  22. Kim, J. Y., Yoon, Y. D., Ahn, J. M., Kang, J. S., Park, S. K., Lee, K., Song, K. B., Kim, H. M. and Han, S. B. (2007). Angelan isolated from Angelica gigas Nakai induces dendritic cell maturation through toll-like receptor 4. Int. Immunopharmacol. 7, 78-87 https://doi.org/10.1016/j.intimp.2006.08.017
  23. Latini, G., Verrotti, A., Manco, R., Scardapane, A., Del Vecchio, A. and Chiarelli, F. (2008). Topiramate: its pharmacological properties and therapeutic efficacy in epilepsy. Mini. Rev. Med. Chem. 8, 10-23 https://doi.org/10.2174/138955708783331568
  24. Luciano, A. L. and Shorvon, S. D. (2007). Results of treatment changes in patients with apparently drug-resistant chronic epilepsy. Ann. Neurol. 62, 375-381 https://doi.org/10.1002/ana.21064
  25. Lyseng-Williamson, K. A. and Yang, L. P. (2007). Topiramate: a review of its use in the treatment of epilepsy. Drugs 67, 2231-2256 https://doi.org/10.2165/00003495-200767150-00008
  26. Lyseng-Williamson, K. A. and Yang, L. P. (2008). Spotlight on topiramate in epilepsy. CNS Drugs 22, 171-174 https://doi.org/10.2165/00023210-200822020-00007
  27. Maryanoff, B. E., Nortey, S. O., Gardocki, J. F., Shank, R. P. and Dodgson, S. P. (1987). Anticonvulsant O-alkyl sulfamates. 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate and related compounds. J. Med. Chem. 30, 880-887 https://doi.org/10.1021/jm00388a023
  28. Moon, E. Y., Oh, S. Y., Han, G. H., Lee, C. S. and Park, S. K. (2005). Epac1-mediated Rap1 activation is not required for the production of nitric oxide in BV2, murine microglial cells. J. Neurosci. Res. 81, 38-44 https://doi.org/10.1002/jnr.20535
  29. Park, H. J., Kim, H. J., Park, H. J., Ra, J., Zheng, L. T., Yim, S. V. and Chung, J. H. (2008). Protective effect of topiramate on kainic acid-induced cell death in mice hippocampus. Epilepsia 49, 163-167 https://doi.org/10.1111/j.1528-1167.2007.01308.x
  30. Peltola, J., Palmio, J., Korhonen, L., Suhonen, J., Miettinen, A., Hurme, M., Lindholm, D. and Keranen, T. (2000). Interleukin-6 and interleukin-1 receptor antagonist in cerebrospinal fluid from patients with recent tonic-clonic seizures. Epilepsy Res. 41, 205-211 https://doi.org/10.1016/S0920-1211(00)00140-6
  31. Privitera, M., Fincham, R., Penry, J., Reife, R., Kramer, L., Pledger, G. and Karim, R. (1996). Topiramate placebocontrolled dose-ranging trial in refractory partial epilepsy using 600-, 800-, and 1,000-mg daily dosages. Topiramate YE Study Group. Neurology 46, 1678-1683 https://doi.org/10.1212/WNL.46.6.1678
  32. Rosenfeld, W. E. (1997). Topiramate: a review of preclinical, pharmacokinetic, and clinical data. Clin. Ther. 19, 1294-1308 https://doi.org/10.1016/S0149-2918(97)80006-9
  33. Rosenfeld, W. E., Doose, D. R., Walker, S. A. and Nayak, R. K. (1997). Effect of topiramate on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in patients with epilepsy. Epilepsia 38, 317-323 https://doi.org/10.1111/j.1528-1157.1997.tb01123.x
  34. Sachdeo, R. C., Sachdeo, S. K., Levy, R. H., Streeter, A. J., Bishop, F. E., Kunze, K. L., Mather, G. G., Roskos, L. K., Shen, D. D., Thummel, K. E., Trager, W. F., Curtin, C. R., Doose, D. R., Gisclon, L. G. and Bialer, M. (2002). Topiramate and phenytoin pharmacokinetics during repetitive monotherapy and combination therapy to epileptic patients. Epilepsia 43, 691-696 https://doi.org/10.1046/j.1528-1157.2002.41701.x
  35. Sharief, M., Viteri, C., Ben-Menachem, E., Weber, M., Reife, R., Pledger, G. and Karim, R. (1996). Double-blind, placebocontrolled study of topiramate in patients with refractory partial epilepsy. Epilepsy Res. 25, 217-224 https://doi.org/10.1016/S0920-1211(96)00029-0
  36. Shorvon, S. D. (1996). Safety of topiramate: adverse events and relationships to dosing. Epilepsia 37(Suppl 2), S18-S22 https://doi.org/10.1111/j.1528-1157.1996.tb06029.x
  37. Tassinari, C. A., Michelucci, R., Chauvel, P., Chodkiewicz, J., Shorvon, S., Henriksen, O., Dam, M., Reife, R., Pledger, G. and Karim, R. (1996). Double-blind, placebo-controlled trial of topiramate (600 mg daily) for the treatment of refractory partial epilepsy. Epilepsia 37, 763-768 https://doi.org/10.1111/j.1528-1157.1996.tb00649.x
  38. Wasserstein, M. L. and Hedges, D. W. (1995). Nephrolithiasis during treatment with topiramate. Epilepsia 36, 153
  39. White, H. S. (1997). Clinical significance of animal seizure models and mechanism of action studies of potential antiepileptic drugs. Epilepsia 38(Suppl 1), S9-17 https://doi.org/10.1111/j.1528-1157.1997.tb04523.x
  40. White, H. S., Brown, S. D., Woodhead, J. H., Skeen, G. A. and Wolf, H. H. (1997). Topiramate enhances GABA-mediated chloride flux and GABA-evoked chloride currents in murine brain neurons and increases seizure threshold. Epilepsy Res. 28, 167-179 https://doi.org/10.1016/S0920-1211(97)00045-4
  41. Yen, D. J., Yu, H. Y., Guo, Y. C., Chen, C., Yiu, C. H. and Su, M. S. (2000). A double-blind, placebo-controlled study of topiramate in adult patients with refractory partial epilepsy. Epilepsia 41, 1162-1166 https://doi.org/10.1111/j.1528-1157.2000.tb00321.x