DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20181646

Study of anticonvulsant activity of acetazolamide on albino rats and its influence on anticonvulsant activity of sodium valproate

Hemanth Kumar K. H., Kishore M. S.

Abstract


Background: Epilepsy is a common neurological disorder. 30-40% of patients will continue to have seizures despite the use of antiepileptic drugs either alone or in combination. The present study is undertaken to evaluate the anticonvulsant activity of Acetazolamide (ACZ) in albino rats and its influence on anticonvulsant activity of sodium valproate.

Methods: Albino rats (150-200gms) of male sex were randomly selected, from central animal facility, MMCRI, Mysore. They were divided into 6groups (per model) of 6 rats each, control group-normal saline 0.5ml, standard group-sodium valproate (300mg/kg), dose 1-ACZ (8.75mg/kg), dose 2-ACZ (17.5mg/kg) and dose 3-ACZ (35mg/kg), dose 4-ACZ (8.75mg/kg) with sodium valproate (150mg/kg). The anti-convulsant activity was screened using MES model and PTZ model.

Results: Results were analysed by ANOVA followed by post hoc Fisher’s LSD test. The ACZ has shown anticonvulsant activity at the dose of 17.5mg/kg and 35mg/kg body weight and combination of ACZ 8.75mg/kg with sodium valproate 150mg/kg both in MES model and PTZ model. The anticonvulsant activity of ACZ was less when compared to Sodium Valproate in both MES model and PTZ model. The anticonvulsant activity of combination, ACZ 8.75mg/kg with Sodium valproate 150mg/kg was comparable and more significant when compared to standard drug alone in MES model and PTZ model.

Conclusions: The ACZ has shown anticonvulsant activity in MES model and PTZ induced seizure model of epilepsy. This study has shown that ACZ potentiated the effect of sodium valproate and can be used as add on drug with sodium valproate in epilepsy.


Keywords


Acetazolamide, Epilepsy, Maximal electroshock seizure model, Nephrotoxicity, Pentylene tetrazole, Tonic hind limb extension

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References


Daniel H. Lowenstein. Seizures and epilepsy. Harrisons Principles of Internal Medicine, 17th Ed. Mc Graw Hill; 2009:2498-2513.

Satoskar RS, Bhendarkar SD, Rege NN. Pharmacology and Pharmacotherapeutics. 19th Ed. Popular Prakashan; 2005:122-140.

Desai CK. Comparative evaluation of anticonvulsant activity of calcium channel blockers in experimental animals. Indian J Exp Biol. 1995;33:931-34.

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

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

Woodbury L.A and V.D Davenport. Archives International pharmacodynamic and therapie. 1952;92:97-107.

Castel-Branco MM, Alves GL, Figueiredo IV, Falcão A, Caramona MM. The maximal electroshock seizure (MES) model in the preclinical assessment of potential new antiepileptic drugs. 2009;31(1):101-6.

Godman LS, Toman JEP, Swinyard EA. Comparison of Maximal seizures evoked by PTZ and electroshock in mice and their modification by anticonvulsant. J pharmacy pharmacology. 1953:168-76.

Michael A, Roger R, Porter J. Antiepileptic drugs: pharmacological Mechanisms and Clinical efficacy with consideration of promising developmental stage compounds. Pharmacol Rev. 1990;42(3):224.

James JEP, James EP, Grey ME. Anticonvulsants In evaluation of drug activities pharmacometrics. Volume I. Laurence DR, Bacharahah ARI (Eds.). London. Academic press;1964:287.

Brahmane RI, Wanmali VV, Pathak SS, Salwe KJ. Role of cinnarizine and nifedipine on anticonvulsant effect of sodium valproate and carbamazepine in maximal electroshock and pentylenetetrazole model of seizures in mice. J pharmacol Pharmacothera. 2010;1(2):78.

Rehni AK, Singh N. Reversal of pentylenetetrazole-induced seizure activity in mice by nickel chloride. Indian J Pharmacol. 2009;41(1):15.

Anderson RE, Chiu P, Woodbury DM. mechanism of tolerance to the anticonvulsant effects of acetazolamide in mice: relation to the activity and amount of carbonic anhydrase in brain. Epilepsia. 1989;30(2):208-16.

Sabers A, Gram L. Drug treatment of epilepsy in the 1990s-achievements and new developments. Drugs. 1996;52:483-93.

Pellock JM. Antiepileptic drug-therapy in the United-States-a review of clinical-studies and unmet needs. Neurology. 1995;45:S17-S24.

Loscher, W. New visions in the pharmacology of anticonvulsion. Euro J Pharmacol. 1998;342:1-13.

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

Swinyard EA, Brown WC,Goodman LSJ. Pharmacol Exp Ther. 1952;106:319-30.

Vogel HG, editor. Drug discovery and evaluation: pharmacological assays. 3rd Edi. Springer Science & Business Media; 2008:673.