Research Article
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Year 2025, Volume: 38 Issue: 1, 68 - 75, 29.01.2025
https://doi.org/10.5472/marumj.1629028

Abstract

References

  • Duncan JS, Sander JW, Sisodiya SM, et al. Adult epilepsy. Lancet 2006;367:1087-100. doi: 10.1016/S0140-6736(06)68477-8
  • Thijs RD, Surges R, O’Brien TJ, et al. Epilepsy in adults. Lancet 2019;393:689-701. doi: 10.1016/S0140-6736(18)32596-0
  • Beghi E. The epidemiology of epilepsy. Neuroepidemiology 2020;54:185-91. doi: 10.1159/000503831
  • Albuja AC, Khan GQ. Absence seizure. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. Accessed on
  • Powell KL, Tang H, Ng C, et al. Seizure expression, behavior, and brain morphology differences in colonies of genetic absence epilepsy rats from Strasbourg. Epilepsia 2014;55:1959- 68. doi: 10.1111/epi.12840
  • Depaulis A, Charpier S. Pathophysiology of absence epilepsy: insights from genetic models. Neurosci Lett 2018;667:53-65. doi: 10.1016/j.neulet.2017.02.035
  • Depaulis A, David O, Charpier S. The genetic absence epilepsy rat from Strasbourg as a model to decipher the neuronal and network mechanisms of generalized idiopathic epilepsies. J Neurosci Methods 2016;260:159-74. doi: 10.1016/j. jneumeth.2015.05.022
  • Ghasemi M, Schachter SC. The NMDA receptor complex as a therapeutic target in epilepsy: a review. Epilepsy Behav 2011;22:617-40. doi: 10.1016/j.yebeh.2011.07.024
  • Prakriya M, Mennerick S. Selective depression of low-release probability excitatory synapses by sodium channel blockers. Neuron 2000;26:671-82. doi: 10.1016/s0896-6273(00)81203-9
  • Yoshida M, Noguchi E, Tsuru N, et al. Effect of riluzole on the acquisition and expression of amygdala kindling. Epilepsy Res 2001;46:101-9. doi: 10.1016/s0920-1211(01)00251-0
  • Lazarevic V, Yang Y, Ivanova D, et al. Riluzole attenuates the efficacy of glutamatergic transmission by interfering with the size of the readily releasable neurotransmitter pool. Neuropharmacology 2018;143:38-48. doi: 10.1016/j. neuropharm.2018.09.021
  • Mollá B, Heredia M, Campos Á, et al. Pharmacological modulation of glutamatergic and neuroinflammatory pathways in a Lafora disease mouse model. Mol Neurobiol 2022;59:6018-32. doi: 10.1007/s12035.022.02956-7
  • Debono MW, Le Guern J, Canton T, et al. Inhibition by riluzole of electrophysiological responses mediated by rat kainate and NMDA receptors expressed in Xenopus oocytes. Eur J Pharmacol 1993;235:283-9. doi: 10.1016/0014- 2999(93)90147-a
  • He Y, Benz A, Fu T, et al. Neuroprotective agent riluzole potentiates postsynaptic GABA(A) receptor function. Neuropharmacology 2002;42:199-209. doi: 10.1016/s0028- 3908(01)00175-7
  • Tidball AM, Lopez-Santiago LF, Yuan Y, et al. Variantspecific changes in persistent or resurgent sodium current in SCN8A-related epilepsy patient-derived neurons. Brain 2020;143:3025-40. doi: 10.1093/brain/awaa247
  • Doble A. The pharmacology and mechanism of action of riluzole. Neurology 1996;47:S233-41. doi: 10.1212/wnl.47.6_ suppl_4.233s
  • Park KM, Kim SE, Lee BI. Antiepileptic drug therapy in patients with drug-resistant epilepsy. J Epilepsy Res 2019;9:14- 26. doi: 10.14581/jer.19002
  • Tekin N, Karamahmutoğlu TE, Aykaç A, et al. The α2Cadrenoceptor antagonist JP-1302 controls behavioral parameters, tyrosine hydroxylase activity, and receptor expression in a rat model of ketamine-induced schizophrenialike deficits. Pharmacol Biochem Behav 2022;221:173490. doi: 10.1016/j.pbb.2022.173490
  • Duprat F, Lesage F, Patel AJ, et al. The neuroprotective agent riluzole activates the two P domain K(+) channels TREK-1 and TRAAK. Mol Pharmacol 2000;57:906-12.
  • Romettino S, Lazdunski M, Gottesmann C. Anticonvulsant and sleep-waking influences of riluzole in a rat model of absence epilepsy. Eur J Pharmacol 1991;199:371-3. doi: 10.1016/0014-2999(91)90503-i
  • Zgrajka W, Nieoczym D, Czuczwar M, et al. Evidences for pharmacokinetic interaction of riluzole and topiramate with pilocarpine in pilocarpine-induced seizures in rats. Epilepsy Res 2010;88:269-74. doi: 10.1016/j.eplepsyres.2009.11.010
  • Zona C, Cavalcanti S, De Sarro G, et al. Kainate-induced currents in rat cortical neurons in culture are modulated by riluzole. Synapse 2002;43:244-51. doi: 10.1002/syn.10040
  • Workman RL Jr, Swinyard EA, Rigby OF, et al. Correlation between anticonvulsant activity and plasma concentration of ethanol. J Am Pharm Assoc Am Pharm Assoc 1958;47:769-72. doi: 10.1002/jps.303.047.1103
  • Golmohammadi R, Pejhan A, Azhdari-Zarmehri H, et al. The role of ethanol on the anticonvulsant effect of valproic acid and cortical microvascular changes after epileptogenesis in mice. Neurol Sci 2013;34:1125-31. doi: 10.1007/s10072.012.1190-y
  • Borowicz KK, Sekowski A, Drelewska E, et al. Riluzole enhances the anti-seizure action of conventional antiepileptic drugs against pentetrazole-induced convulsions in mice. Pol J Pharmacol 2004;56:187-93.
  • Jadhav AR, Vakade KP, Nayak BB, et al. The effect of riluzole alone and in combination with sodium valproate on pentylenetetrazole induced seizures in swiss-albino rats. Int J Basic Clin Pharmacol 2016;5:728-32. doi: 10.18203/2319- 2003.ijbcp20161509

Evaluation of isolated and combined effects of riluzole and sodium valproate in genetic absence epilepsy rats

Year 2025, Volume: 38 Issue: 1, 68 - 75, 29.01.2025
https://doi.org/10.5472/marumj.1629028

Abstract

Objective: In epilepsy treatment, drugs that increase GABAergic and decrease glutamatergic activity, like sodium valproate, are used.
Riluzole is a neuroprotective drug that blocks glutamatergic neurotransmission and is a potential drug with its anti-seizure effects. This
study evaluates the anti-seizure effects of sodium valproate and riluzole on the genetic absence epilepsy rat from Strasbourg (GAERS)
model individually and combined.
Materials and Methods: Adult male GAERS rats (n = 22) were used. Rats were administered 5/10 mg/kg riluzole, 150/300 mg/kg
sodium valproate, 95% ethanol, and 5 mg/kg riluzole combinations with 150-300 mg/kg sodium valproate intraperitoneally. EEG
recordings and locomotor activity tests were conducted. Statistical analysis was performed using GraphPad Prism.
Results: Post-injection of 10 mg/kg riluzole significantly decreased the number of spike-wave-discharges (SWDs) (p = 0.04) compared
to the control group. A synergistic effect was observed with 5 mg/kg riluzole and 150 mg/kg sodium valproate, reducing total seizure
time (p = 0.03) and SWDs (p = 0.03).
Conclusion: The study demonstrated the anti-seizure effects of 150/300 mg/kg sodium valproate, 10 mg/kg riluzole, and ethanol. A
synergistic effect of 5 mg/kg riluzole with 150 mg/kg sodium valproate was noted. As an isolated or combined solution, riluzole shows
potential, especially in resistant epilepsy treatment.

References

  • Duncan JS, Sander JW, Sisodiya SM, et al. Adult epilepsy. Lancet 2006;367:1087-100. doi: 10.1016/S0140-6736(06)68477-8
  • Thijs RD, Surges R, O’Brien TJ, et al. Epilepsy in adults. Lancet 2019;393:689-701. doi: 10.1016/S0140-6736(18)32596-0
  • Beghi E. The epidemiology of epilepsy. Neuroepidemiology 2020;54:185-91. doi: 10.1159/000503831
  • Albuja AC, Khan GQ. Absence seizure. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. Accessed on
  • Powell KL, Tang H, Ng C, et al. Seizure expression, behavior, and brain morphology differences in colonies of genetic absence epilepsy rats from Strasbourg. Epilepsia 2014;55:1959- 68. doi: 10.1111/epi.12840
  • Depaulis A, Charpier S. Pathophysiology of absence epilepsy: insights from genetic models. Neurosci Lett 2018;667:53-65. doi: 10.1016/j.neulet.2017.02.035
  • Depaulis A, David O, Charpier S. The genetic absence epilepsy rat from Strasbourg as a model to decipher the neuronal and network mechanisms of generalized idiopathic epilepsies. J Neurosci Methods 2016;260:159-74. doi: 10.1016/j. jneumeth.2015.05.022
  • Ghasemi M, Schachter SC. The NMDA receptor complex as a therapeutic target in epilepsy: a review. Epilepsy Behav 2011;22:617-40. doi: 10.1016/j.yebeh.2011.07.024
  • Prakriya M, Mennerick S. Selective depression of low-release probability excitatory synapses by sodium channel blockers. Neuron 2000;26:671-82. doi: 10.1016/s0896-6273(00)81203-9
  • Yoshida M, Noguchi E, Tsuru N, et al. Effect of riluzole on the acquisition and expression of amygdala kindling. Epilepsy Res 2001;46:101-9. doi: 10.1016/s0920-1211(01)00251-0
  • Lazarevic V, Yang Y, Ivanova D, et al. Riluzole attenuates the efficacy of glutamatergic transmission by interfering with the size of the readily releasable neurotransmitter pool. Neuropharmacology 2018;143:38-48. doi: 10.1016/j. neuropharm.2018.09.021
  • Mollá B, Heredia M, Campos Á, et al. Pharmacological modulation of glutamatergic and neuroinflammatory pathways in a Lafora disease mouse model. Mol Neurobiol 2022;59:6018-32. doi: 10.1007/s12035.022.02956-7
  • Debono MW, Le Guern J, Canton T, et al. Inhibition by riluzole of electrophysiological responses mediated by rat kainate and NMDA receptors expressed in Xenopus oocytes. Eur J Pharmacol 1993;235:283-9. doi: 10.1016/0014- 2999(93)90147-a
  • He Y, Benz A, Fu T, et al. Neuroprotective agent riluzole potentiates postsynaptic GABA(A) receptor function. Neuropharmacology 2002;42:199-209. doi: 10.1016/s0028- 3908(01)00175-7
  • Tidball AM, Lopez-Santiago LF, Yuan Y, et al. Variantspecific changes in persistent or resurgent sodium current in SCN8A-related epilepsy patient-derived neurons. Brain 2020;143:3025-40. doi: 10.1093/brain/awaa247
  • Doble A. The pharmacology and mechanism of action of riluzole. Neurology 1996;47:S233-41. doi: 10.1212/wnl.47.6_ suppl_4.233s
  • Park KM, Kim SE, Lee BI. Antiepileptic drug therapy in patients with drug-resistant epilepsy. J Epilepsy Res 2019;9:14- 26. doi: 10.14581/jer.19002
  • Tekin N, Karamahmutoğlu TE, Aykaç A, et al. The α2Cadrenoceptor antagonist JP-1302 controls behavioral parameters, tyrosine hydroxylase activity, and receptor expression in a rat model of ketamine-induced schizophrenialike deficits. Pharmacol Biochem Behav 2022;221:173490. doi: 10.1016/j.pbb.2022.173490
  • Duprat F, Lesage F, Patel AJ, et al. The neuroprotective agent riluzole activates the two P domain K(+) channels TREK-1 and TRAAK. Mol Pharmacol 2000;57:906-12.
  • Romettino S, Lazdunski M, Gottesmann C. Anticonvulsant and sleep-waking influences of riluzole in a rat model of absence epilepsy. Eur J Pharmacol 1991;199:371-3. doi: 10.1016/0014-2999(91)90503-i
  • Zgrajka W, Nieoczym D, Czuczwar M, et al. Evidences for pharmacokinetic interaction of riluzole and topiramate with pilocarpine in pilocarpine-induced seizures in rats. Epilepsy Res 2010;88:269-74. doi: 10.1016/j.eplepsyres.2009.11.010
  • Zona C, Cavalcanti S, De Sarro G, et al. Kainate-induced currents in rat cortical neurons in culture are modulated by riluzole. Synapse 2002;43:244-51. doi: 10.1002/syn.10040
  • Workman RL Jr, Swinyard EA, Rigby OF, et al. Correlation between anticonvulsant activity and plasma concentration of ethanol. J Am Pharm Assoc Am Pharm Assoc 1958;47:769-72. doi: 10.1002/jps.303.047.1103
  • Golmohammadi R, Pejhan A, Azhdari-Zarmehri H, et al. The role of ethanol on the anticonvulsant effect of valproic acid and cortical microvascular changes after epileptogenesis in mice. Neurol Sci 2013;34:1125-31. doi: 10.1007/s10072.012.1190-y
  • Borowicz KK, Sekowski A, Drelewska E, et al. Riluzole enhances the anti-seizure action of conventional antiepileptic drugs against pentetrazole-induced convulsions in mice. Pol J Pharmacol 2004;56:187-93.
  • Jadhav AR, Vakade KP, Nayak BB, et al. The effect of riluzole alone and in combination with sodium valproate on pentylenetetrazole induced seizures in swiss-albino rats. Int J Basic Clin Pharmacol 2016;5:728-32. doi: 10.18203/2319- 2003.ijbcp20161509
There are 26 citations in total.

Details

Primary Language English
Subjects Surgery (Other)
Journal Section Original Research
Authors

Tuğba Karamahmutoğlu 0000-0002-0124-159X

Eren Şahin 0000-0002-9590-797X

Bahattin Gürbüz 0009-0000-5765-6981

Türkan Şükürov This is me 0000-0001-8936-0288

Ayşe Nazlı Güneş This is me 0009-0005-5275-7077

Ege Fakı This is me 0009-0003-8900-8622

Rezzan Gülhan 0000-0002-1519-3170

Zeynep Us This is me 0000-0001-5139-7691

Publication Date January 29, 2025
Submission Date January 24, 2024
Acceptance Date September 6, 2024
Published in Issue Year 2025 Volume: 38 Issue: 1

Cite

APA Karamahmutoğlu, T., Şahin, E., Gürbüz, B., Şükürov, T., et al. (2025). Evaluation of isolated and combined effects of riluzole and sodium valproate in genetic absence epilepsy rats. Marmara Medical Journal, 38(1), 68-75. https://doi.org/10.5472/marumj.1629028
AMA Karamahmutoğlu T, Şahin E, Gürbüz B, Şükürov T, Güneş AN, Fakı E, Gülhan R, Us Z. Evaluation of isolated and combined effects of riluzole and sodium valproate in genetic absence epilepsy rats. Marmara Med J. January 2025;38(1):68-75. doi:10.5472/marumj.1629028
Chicago Karamahmutoğlu, Tuğba, Eren Şahin, Bahattin Gürbüz, Türkan Şükürov, Ayşe Nazlı Güneş, Ege Fakı, Rezzan Gülhan, and Zeynep Us. “Evaluation of Isolated and Combined Effects of Riluzole and Sodium Valproate in Genetic Absence Epilepsy Rats”. Marmara Medical Journal 38, no. 1 (January 2025): 68-75. https://doi.org/10.5472/marumj.1629028.
EndNote Karamahmutoğlu T, Şahin E, Gürbüz B, Şükürov T, Güneş AN, Fakı E, Gülhan R, Us Z (January 1, 2025) Evaluation of isolated and combined effects of riluzole and sodium valproate in genetic absence epilepsy rats. Marmara Medical Journal 38 1 68–75.
IEEE T. Karamahmutoğlu, E. Şahin, B. Gürbüz, T. Şükürov, A. N. Güneş, E. Fakı, R. Gülhan, and Z. Us, “Evaluation of isolated and combined effects of riluzole and sodium valproate in genetic absence epilepsy rats”, Marmara Med J, vol. 38, no. 1, pp. 68–75, 2025, doi: 10.5472/marumj.1629028.
ISNAD Karamahmutoğlu, Tuğba et al. “Evaluation of Isolated and Combined Effects of Riluzole and Sodium Valproate in Genetic Absence Epilepsy Rats”. Marmara Medical Journal 38/1 (January 2025), 68-75. https://doi.org/10.5472/marumj.1629028.
JAMA Karamahmutoğlu T, Şahin E, Gürbüz B, Şükürov T, Güneş AN, Fakı E, Gülhan R, Us Z. Evaluation of isolated and combined effects of riluzole and sodium valproate in genetic absence epilepsy rats. Marmara Med J. 2025;38:68–75.
MLA Karamahmutoğlu, Tuğba et al. “Evaluation of Isolated and Combined Effects of Riluzole and Sodium Valproate in Genetic Absence Epilepsy Rats”. Marmara Medical Journal, vol. 38, no. 1, 2025, pp. 68-75, doi:10.5472/marumj.1629028.
Vancouver Karamahmutoğlu T, Şahin E, Gürbüz B, Şükürov T, Güneş AN, Fakı E, Gülhan R, Us Z. Evaluation of isolated and combined effects of riluzole and sodium valproate in genetic absence epilepsy rats. Marmara Med J. 2025;38(1):68-75.