Anticonvulsant activity of atorvastatin against seizure induced by pentylenetetrazole and maximal electroshock in mice

Document Type: Research(Original) Article



Statins are inhibitors of HMG-CoA reductase and inhibit cellular synthesis of cholesterol and isoprenoids. Studies have previously demonstrated the anti-inflammatory and vasoprotective effects of statins on cultured brain cells (astrocytes and microglia) and endothelial cells. Statins have been recently recognized as anti-inflammatory and neuroprotective drugs. Later, neuroprotective effects of statin were reported in various animal disease models and clinical studies. Atorvastatin also prolonged latency (time to appearance of spike potentials) and diminished the amplitude and frequency of spike potentials, which indicate epileptic discharges. In some studies observed that pre-treatment with atorvastatin efficiently reduced seizure activities, hippocampal neuron death, monocyte infiltration and proinflammatory gene expression. In this study the protective effects of atorvastatin on seizures induced by Pentylenetetrazolee (PTZ) and maximal electroshock stimulation (MES) were investigated. Intraperitoneal pentylenetetrazole was used to induce seizures in mice.It was found that atorvastatin (ED50 = 5.12±0.98) has antiseizure effects comparing to control group. Atorvastatin treatment significantly increased the seizure threshold (p<0.01) and decreased the incidence of tonic seizure and death which is induced by intraperitoneal pentylenetetrazole . The effect of atorvastatin on seizure induced by MES in mice was evaluated and the results demonstrated it is not able to produce anticonvulsant activity.Key word: Seizure, Atorvastatin, Pentylenetetrazole, Maximal electroshock.

  1. Üzüm G, Akgün-Dar K, Aksu U. The effects of atorvastatin on memory deficit and seizure susceptibility in pentylentetrazole-kindled rats. Epilepsy Behav. 2010;19(3):284-9. PMID: 20888302 [PubMed - indexed for MEDLINE], doi: 10.1016/j.yebeh.2010.07.024
  2. Sayyah M, Moaied S, Kamalinejad M. Anticonvulsant activity of Heracleum persicum seed. J Ethnopharmacol. 2005;98(1-2):209-11. PMID: 15763386 [PubMed - indexed for MEDLINE], DOI: 10.1016/j.jep.2004.12.026
  3. Bum EN, Schmutz M, Meyer C, Rakotonirina A, Bopelet M, Portet C, et al. Anticonvulsant properties of the methanolic extract of Cyperus articulatus (Cyperaceae). J Ethnopharmacol. 2001;76(2):145-50. PMID: 11390127 [PubMed - indexed for MEDLINE], DOI: 10.1016/S0378-8741(01)00192-1
  4. Sayysah M, Mandgary A, Kamalinejad M. Evaluation of the anticonvulsant activity of the seed acetone extract of Ferula gummosa Boiss.against seizure induced by pentylenetetrazolee and electroconvulsive shock in mice. J Ethnopharmacol. 2002;82(2-3):105-9. PMID: 12241984 [PubMed - indexed for MEDLINE], DOI: 10.1016/S0378-8741(02)00166-6
  5. Wang CY, Liu PY, Liao JK. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends mol med. 2008;14(1):37-44. PMID: 18068482 [PubMed - indexed for MEDLINE], PMCID: PMC2621332, DOI: 10.1016/j.molmed.2007.11.004
  6. Palinsk W. New evidence for beneficial effects of statins unrelated to lipid lowering. Arterioscler Thromb Vasc Biol. 2001;21(1):3-5. PMID: 11145927 [PubMed - indexed for MEDLINE], Doi: 10.1161/01.ATV.21.1.3
  7. Rajanikant G, Zemke D, Kassab M, Majid A. The therapeutic potential of statins in neurological disorders. Curr Med Chem. 2007;14(1):103-12. PMID: 17266571 [PubMed - indexed for MEDLINE], DOI: 10.2174/092986707779313462
  8. Kureishi Y, Luo Z, Shiojima I, Bialik A, Fulton D, Lefer DJ, et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med. 2000;6(9):1004. PMID: 10973320 [PubMed - indexed for MEDLINE], PMCID: PMC2828689, Doi: 10.1038/79510
  9. Shimamura M, Sato N, Sata M, Kurinami H, Takeuchi D, Wakayama K, et al. Delayed postischemic treatment with fluvastatin improved cognitive impairment after stroke in rats. Stroke. 2007;38(12):3251-8. PMID: 17975105 [PubMed - indexed for MEDLINE], Doi: 10.1161/STROKEAHA.107.485045
  10. Vaughan CJ. Prevention of stroke and dementia with statins: effects beyond lipid lowering. Am J Cardiol. 2003;91(4):23-9. PMID: 12615295 [PubMed - indexed for MEDLINE], DOI: 10.1016/S0002-9149(02)03270-8
  11. Bösel J, Gandor F, Harms C, Synowitz M, Harms U, Djoufack PC, et al. Neuroprotective effects of atorvastatin against glutamate‐induced excitotoxicity in primary cortical neurones. J Neurochem. 2005;92(6):1386-98. PMID: 15748157 [PubMed - indexed for MEDLINE], DOI: 10.1111/j.1471-4159.2004.02980.x
  12. Lee JK, Won JS, Singh AK, Singh I. Statin inhibits kainic acid-induced seizure and associated inflammation and hippocampal cell death. Neurosci Lett. 2008;440(3):260-4. PMID: 18583044 [PubMed - indexed for MEDLINE], PMCID: PMC2702849, DOI: 10.1016/j.neulet.2008.05.112
  13. Moazzami K, Emamzadeh‐Fard S, Shabani M. Anticonvulsive effect of atorvastatin on pentylenetetrazolee‐induced seizures in mice: the role of nitric oxide pathway. Fundam Clin Pharmacol. 2012; 27(4), 387–392, PMID: 22429218 [PubMed - indexed for MEDLINE], DOI: 10.1111/j.1472-8206.2012.01038.x