The effect of riluzole alone and in combination with sodium valproate on pentylenetetrazole induced seizures in swiss-albino rats

Authors

  • Amol Ramrao Jadhav Department of Pharmacology, PDVVPF’s Medical College, Ahmednagar, Maharashtra, India
  • Kiran Prabhakar Vakade Department of Pharmacology, PDVVPF’s Medical College, Ahmednagar, Maharashtra, India
  • Bana Bihari Nayak Department of Pharmacology, PDVVPF’s Medical College, Ahmednagar, Maharashtra, India
  • Vijayaprasad M. Sangisetti Department of Pharmacology, PDVVPF’s Medical College, Ahmednagar, Maharashtra, India
  • Vijaykumar N. Abhavathi Department of Pharmacology, PDVVPF’s Medical College, Ahmednagar, Maharashtra, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20161509

Keywords:

Riluzole, PTZ induced seizure, Antiepileptic, Convulsions

Abstract

Background: Riluzole- a glutamate antagonist is known to enhance antiepileptic effects of various other antiepileptic drugs. The present study was undertaken to evaluate anticonvulsant effect of riluzole alone and in combination with sodium valproate on pentylenetetrazole (Metrazol) induced seizures in swiss-albino rats.

Methods: Pentylenetetrazole (PTZ) 50 mg/kg intraperitonially (ip) was used to induce seizure in swiss- albino rats. Anticonvulsant effect of riluzole (at 5 mg/kg and 10 mg/kg) and sodium valproate (at 75 mg/kg, 150 mg/kg and 300 mg/kg) was studied on PTZ induced seizures in albino rats. Also effect of riluzole (10mg/kg) in combination with sodium valproate (75 mg/kg, 150 mg/kg and 300 mg/kg) was studied.  Parameters such as time of onset of first clonic convulsion in seconds, frequency of clonic convulsion in 60 minute and total duration of entire convulsion in minutes were studied. For statistical analysis unpaired t test was used.

Results: At 5 mg/kg and 10 mg/kg doses riluzole per se was not found to produce any significant effect in PTZ induced seizures (P>0.05). Sodium valproate at 300 mg/kg dose was found to produce significant antiepileptic effect (P<0.001) but not at 75 mg/kg and 150 mg/kg dose (P>0.05). Interestingly significant antiepileptic effect was noted with combination of riluzole (at 10 mg/kg) with sodium valproate at 150 mg/kg and 300 mg/kg dose (P<0.001).

Conclusions: Riluzole alone was not found to produce any significant protective effect against PTZ induced seizures in albino rats. However riluzole (10 mg/kg) was found to enhance the antiepileptic activity of sodium valproate.

References

Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. A practical clinical definition of epilepsy. ILAE official report. Epilepsia. 2014;55(4):475-82.

Fischer RS, Boas WE, Blume W, Elger C, Genton P, Lee P, et al. Epileptic seizures and epilepsy: definitions proposed by the ILAE and the IBE. Epilepsia. 2005;46(4):470-2.

Gopi G, Jayasri P, Elumalali A. Antiepileptic effect of Malachra capitatal. On maximal electro shock (MES) and pentylenetetrazole (PTZ) induced seizures. International Journal of Pharmacology and Toxicology. 2012;2(2):104-8.

Bharucha NE. Epidemiology of epilepsy in India. Epilepsia. 2003;44(1):9-11.

White HS. Preclinical development of antiepileptic drugs: past, present and future directions. Epilepsia. 2003;44(7):2-8.

La Roche SM, Helmers SL. The new antiepileptic drugs. JAMA. 2004;291(5):605.

Borowicz KK, Sekowski A, Drelewska E, Czuczwar SJ. Riluzole enhances the anti-seizure action of conventional anti-epileptic drugs against pentetrazole induced convulsions in mice. Pol. J Pharmacol. 2004;56(2):187-93.

Loscher W. Basic pharmacology of valproate; a review after 35 years of clinical use for the treatment of epilepsy. CNS Drugs. 2002;16(10):669-94.

Beatriz S, Fagundes R. Valproic acid review. REV Neuroscience. 2008;16(2):130-6.

Satoskar RS, Bhendarkar SD, Rege NN. Pharmacology and pharmacotherapeutics. 22nd Ed. Mumbai, India: Popular Prakashan; 2011:124-42.

Khanna N, Bhalla S, Verma V, Sharma KK. Modulatory effects of nifedipine and nimodipine in experimental convulsions. Indian Journal of Pharmacology. 2000;32:347-52.

Malhotra J, Seth SD, Gupta SK, Gupta YK. Adenosinergic mechanisms in anticonvulsant action of diazepam and sodium valproate. Environmental toxicology and pharmacology. 1996;1(4):269-77.

Kretschmer BD, Kratzer U, Schmidt WJ. Riluzole, a glutamate release inhibitor, and motor behavior, Naunyn Schmiedebergs. Arch Pharmacol. 1998;358:181-190.

Malgouris C, Daniel M, Doble A. Neuroprotective effects of riluzole on N-methyl-D-aspartate- or veratridine- induced neurotoxicity in rat hippocampal slices. Neurosci Lett. 1994;177:95-9.

Mizoule J, Meldrum B, Mazadier M, Croucher M, Ollat C, Uzan A, et al. 2-Amino-6-trifluoromethoxy benzothiazole, a possible antagonist of excitatory amino acid neurotransmission. Anticonvulsant properties. Neuro pharmacology. 1985;24:767-73.

De Sarro G, Siniscalchi A, Ferreri G, Gallelli L, De Sarro A. NMDA and AMPA/kainate receptors are involved in the anticonvulsant activity of riluzole in DBA2/mice. Eur J Pharmacol. 2000;408:25-34.

Parsons CG, Danysz W, Quack G. Glutamate in CNS disorders as a target for drug development: an update. Drugs News Perspect. 1998;11:523-69.

Czuczwar SJ, Turski WA, Kleinrok Z. Interaction of calcium channel blockers and excitatory amino acid antagonists with conventional antiepileptic drugs. CNS Drug Rev. 1996;2:452-67.

Downloads

Published

2016-12-30

How to Cite

Jadhav, A. R., Vakade, K. P., Nayak, B. B., Sangisetti, V. M., & Abhavathi, V. N. (2016). The effect of riluzole alone and in combination with sodium valproate on pentylenetetrazole induced seizures in swiss-albino rats. International Journal of Basic & Clinical Pharmacology, 5(3), 728–732. https://doi.org/10.18203/2319-2003.ijbcp20161509

Issue

Section

Original Research Articles