26Jul 2017

Effect of flupirtine on seizure activity and its interactions with antiepileptic drugs in rats.

  • Assistant Professor, Department of Pharmacology, Dr. PDMMC, Amravati.
  • Associate Professor, Dept of Pharmacology, NKPSIMS, Nagpur.
  • Professor & Head Dept of Pharmacology Dr. PDMMC, Amravati.
Crossref Cited-by Linking logo
  • Abstract
  • Keywords
  • References
  • Cite This Article as
  • Corresponding Author

Aims:-To evaluate the effect of flupirtine in maximal electroshock seizures (MES) induced seizures in rats and study the interactions of flupirtine with some antiepileptic drugs, by using subtherapeutic doses. Methods and Material:-The effects were assessed by methods of MES. Results:-Flupirtine alone showed protection against electroshock seizures. Combined treatment of flupirtine and antiepileptic drugs exerted a much stronger protective effect against electroshock seizures than either drug alone or addition of their effect. This was highly significant for a combination of flupirtine with diazepam, sodium valproate, phenobarbitone, and phenytoin. Conclusions:-Flupirtine has anticonvulsant activity and has synergistic activity with antiepileptic drugs in MES model. Extrapolation of these combinations in clinical practice may suggest its utility in grandmal epilepsy as add-on drug.

  1. WHO/ Epilepsy. Fact sheet No 999, October 2012
  2. Chopra JS, Sawhney IMS. Epilepsy in tropics. In Arturo.,Carpio, P R M.& de Bittencourt, editor. Neurology in tropics, New Delhi: BI Churchill Lingstone. Pvt. Ltd Publication;1999, 527-31.
  3. Reddy DS. Pharmacotherapy of catamenial epilepsy. Indian J Pharmacol 2005; 37:288-93.
  4. Kwan, P.; Sander, J.W. The natural history of epilepsy: An epidemiological view. Neurol. Neurosurg. Psychiatry 2004, 75, 1376-1381.
  5. Kornhuber J, Bleich S, Wiltfang J, maler M and Parsons CG. Flupirtine shows functional NMDA receptor antagonism by enhancing Mg2+ block via activation of voltage independent potassium channels. J Neural Transm 1999;106:857-67.
  6. Vogel GH, Vogel WH. Antiepileptic activity. Hans Gerhard Vogel editor. Drug discovery and evaluation: Safety and Pharmacokinetic Assay, 2nd Heidelberg: Springer Publishers; 2002.p.459-93.
  7. Gupta YK, Malhotra J, George B, Kulkarni SK. Methods and considerations for experimental evaluation of antiepileptic drugs. Indian J PhysiolPharmacol 1999;43:25-43.
  8. Swinyard EA, Brown WC, Goodman LS. Comparative assay of antiepileptic drugs in mice and rats. PharmacolExpTher 1952; 106:319-30.
  9. Hill AB, Hill ID. Principles of Medical Statistics, 12th New Delhi: B.I. Publication Pvt Ltd; 1993.p.12-22.
  10. Sunder Rao PSS, Richard J. Introduction to biostatistics and research methods, 4th New Delhi: Prientes Hall of India Pvt Ltd; 2006.p.40-50.
  11. Naveen Kumar M, Gokul CG, Somashekar HS, Adake P, AcharyaA,Santhosh R et al. Anticonvulsant activity of flupirtine in albino mice. Pharmacologyonline 2011;3:860-67.
  12. Raol YH,?Lapides DA,?Keating JG,?Brooks-Kayal AR,?Cooper EC. A KCNQ channel opener for experimental neonatal seizures and status epilepticus. Ann Neurol 2009;65:326-36.
  13. Marylou VS,?Adrian R, Steven LW, George FK. Activators of potassium M currents have anticonvulsant actions in two rat models of encephalitis. Eur J Pharmacol 2007;555:23-29.
  14. Bajrić M, Klinger F, Schandl U, Kubista H, Boehm S. Antiepileptic activity and subtype-selective action of flupirtine at GABAA BMC Pharmacology and Toxicology 2012;13(Suppl 1): A90, Available at: http://www.biomedcentral.com/2050-6511/13/S1/A90
  15. M Current-Based Therapies for Nerve Agent Seizures. University of Virginia, Department of Neurology, Charlottesville 2011, Form Approved OMB No. 0704.
  16. Harish S, Bhuvana K, Girish M, Bengalorkar K. Flupirtine: Clinical pharmacology. J AnaesthesiolClinPharmacol 2012;28:172-77.
  17. Perovic S, Schleger C, Pergande G, Iskric I, Ushijima H, Rytic P, et al. The triamino pyridine flupirtine prevents cell death in rat cortical cells induced by Nmethyl-D-aspartate and gp 120 of HIV-1. Eur J PharmacolMolPharmacol 1994;288:27?33.
  18. Block F, Schwarz M, Pergande G. N-methyl-D-aspartate (NMDA)-mediated muscle relaxant action of flupirtine in rats.Neuroreport 1993;4:941-3.
  19. Osborne NN, Pergande G, Block F, Schwarz M. Immunohistochemical evidence for flupirtine acting as an antagonist on the N-methyl-D-aspartate and homocysteic acid induced release of GABA in the rabbit retina. Brain Res 1994;667:291?94.
  20. Schwarz M, Schmitt T, Pergande G, Block F. N-methyl-D-aspartate and α adrenergic mechanism are involved in the depressant action of flupirtine on spinal reflexes in rats. Eur J Pharmacol 1995;276:247?55.
  21. Banerjee TK, Ray BK, Das SK, Hazra A, Ghosal MK, Chaudhuri A, et al. A longitudinal study of epilepsy in Kolkota, India.?Epilepsia?2010; 51:2384?91.

[B. G. Dudhe, R.T. Badwaik, and A.S. Bhore. (2017); Effect of flupirtine on seizure activity and its interactions with antiepileptic drugs in rats. Int. J. of Adv. Res. 5 (Jul). 1824-1828] (ISSN 2320-5407). www.journalijar.com

Dr. Bhushan Gunvantrao Dudhe
Assistant Professor, Department of Pharmacology, Dr. Panjabrao Deshmukh Memorial Medical College, Amravati

DOI:

Article DOI: 10.21474/IJAR01/4906      
DOI URL: http://dx.doi.org/10.21474/IJAR01/4906

Download Full Paper

Download PDF No. of Downloads: 20 | No. of Views: 104