Screening of the Anticonvulsant Activity of Some Isatin Derivatives in Experimental Seizure Models and Its Effect on Brain GABA Levels in Mice

Venkateshwarlu Eggadi^{1, 2}, Umasankar Kulandaivelu², Sharvanabhava B S² and Venkateshwar Rao Jupally^3,

¹Department of Biotechnology, AcharyaNagarjuna University, Guntur, India

²Vaagdevi College of Pharmacy, Hanamkonda, Warangal, India

³TallaPadmavathi College of Pharmacy, Orus, Warangal, India

Cite this paper:
Venkateshwarlu Eggadi, Umasankar Kulandaivelu, Sharvanabhava B S and Venkateshwar Rao Jupally. Screening of the Anticonvulsant Activity of Some Isatin Derivatives in Experimental Seizure Models and Its Effect on Brain GABA Levels in Mice. American Journal of Pharmacological Sciences. 2013; 1(3):42-46. doi: 10.12691/ajps-1-3-3

Abstract

The modern therapeutic approaches of antiepileptic agents against epileptic patients are showing many side effects, dose related effects and chronic toxicity. The aim of our present work is to evaluate anticonvulsant activity of isatin derivatives (Ia-Ij) to reduce the side-effects and increase the percentage protection from various stages of convulsions. No animals showed toxic effects even up to 2000mg/kg. It is evident that Ib, Ie, Ih, Ii and Ij showed anticonvulsant effect at the dose levels of 10 and 100mg/kg in MES test and except Ij all other derivatives exhibited antiepileptic effect at 10 and 100mg/kg in PTZ induced convulsions test. The isatin derivatives (Ib, Ie, Ih and Ii) which proved antiepileptic effect in both MES and PTZ induced convulsion models are selected and GABA levels in brain were estimated. They showed significant increase of GABA levels in brain.

Keywords:
isatin anticonvulsant activity pentylene tetrazole maximum electric shock GABA

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Sander, J.W, The epidemiology of epilepsy revisited. Curr Opin Neurol, 2003, 165-170.
[2]	Rang, H.P, Dale, M.M, Ritter, J.M. and Moore,P.K, Textbook of Pharmacology. Churchill Livingstone,UK, 2007,575-584.
[3]	Newton, C.R. and Garcia, H.H, Epilepsy in poor regions of the world. Lancet,2012, 1193-1201.
[4]	Kotsopoulos, I.A.W., Van Merode, T., Kessels, F.G.H.,De Krom, M.C.T.F., and Knottnerus, J.A, “Systematic Review and Meta‐analysis of Incidence Studies of Epilepsy and Unprovoked Seizures”, Epilepsia, 43(11).1402-1409.Nov.2002.
[5]	Bell, G.S. and Sander, J .W, CPD-Education and self-assessment the epidemiology of epilepsy: the size of the problem. Seizure, 10(4).306-316. June. 2001.
[6]	Kaur, H., Kumar, S. and Kumar, A, Synthesis, Antipsychotic and Anticonvulsant Activity of some new pyrazolinyl/isoxazolinylindol-2-ones. Int J ChemTech Res, 2(2).1010-1019. April-June.2010.
[7]	Geronikaki, A., Babaev, E., Dearden, J., et al. “Design, synthesis, computational and biological evaluation of new anxiolytics”,Bioorg Med Chem, 12(24). 6559-6568. Sept.2004.
[8]	Gudipati, R. Anreddy, R.N.R. and Manda, S. “Synthesis, characterization and anticancer activity of certain 3-{4-(5-mercapto-1, 3, 4-oxadiazole-2-yl) phenylimino} indolin-2-one derivatives”, Saudi Pharm, 19(3).153-158.July.2011.
[9]	Venkateshwaralu, E., Venkateshwar Rao, J., Umasankar, K. and Dheeraj, G. “Sudy of anti-inflammatory, analgesic and antipyretic activity of novel isatin derivatives”. Asian J Pharm Clin Res, 5(4).187-190. August.2012.
[10]	Rodríguez-Argüelles, M.C., Mosquera-Vázquez, S., Tourón-Touceda, P., Sanmartín-Matalobos, J., García-Deibe, A.M., Belicchi-Ferrari, M., Pelosi, G., Pelizzi, C. and Zani F. “Complexes of 2-thiophenecarbonyl and isonicotinoyl hydrazones of 3-(N-methyl) isatin:A study of their antimicrobial activity”. J Inorg Biochem, 101(1).138-147.Jan. 2007.
[11]	Jiang, T., Kuhen, K.L., Wolff, K., Yin, H., Bieza, K., Caldwell, J., Bursulaya, B., Tuntland, T., Zhang, K., Karanewsky, D. and He Y. “Design, synthesis, and biological evaluations of novel oxindoles as HIV-1 non-nucleoside reverse transcriptase inhibitors”. Bioorg Med Chem Lett, 16(8).2109-2112.Apr.2006.
[12]	Maskell, L., Blanche, E.A., Colucci, M.A., Whatmore, J.L. and Moody, C.J. “Synthesis and evaluation of prodrugs for anti-angiogenic pyrrolylmethylidenyl oxindoles”. Bioorg Med Chem Lett, 17(6).1575-1578. March. 2007.
[13]	Igosheva, N., Lorz, C., O’Conner, E., Glover, V. and Mehmet, H. “Isatin, an endogenous monoamine oxidase inhibitor, triggers a dose- and time-dependent switch from apoptosis to necrosis in human neuroblastoma cells”. Neurochem. Int, 47(3).216-224. Aug.2005.
[14]	Van den Heuvel, M.J., Clark, D.G., Fielder, R.J., Koundakjian, P.P., Oliver, G.J.A., Pelling, D., Tomlinson, N.J. and Walker, A.P, “The international validation of a fixed-dose procedure as an alternative to the classical LD50 test”. Food Chem Toxicol, 28(7).469-482. Jul.1990.
[15]	Turner, R.A, Anticonvulsants. Screening methods in Pharmacology, Academic Press New York, 1965, 64-65.
[16]	Khosla,P. and Pandhi.P, “Anticonvulsant effect of nimodipine alone and in combination with diazepam on PTZ induced status epilepticus”. Indian J Pharmacol, 33.208-211. Sept.2001.
[17]	Swinyard, E.A., Brown, W.C. and Goodman, L.S. “Comparative assays of antiepileptic drugs in mice and rats”. J Pharmacol Exp Ther, 106(3).319-330. Nov.1952.
[18]	Löscher, W. and Schmidt, D. “Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations”. Epilepsy Res, 2(3):145-181.May-June.1988.
[19]	Swinyard, E.A. Electrically induced convulsions. Raven Press, New York,433-458. M.1972.
[20]	Lowe, I.P., Robins, E. and Eyerman, G.S. “The fluorometric measurement of glutamic decarboxylase and its distribution in brain”. J Neurochem, 3(1).8-18.Oct.1958.
[21]	Katzung, B.G. Basic and Clinical Pharmacology. McGraw Hill, New York, 2009. 357-369.
[22]	Tripathi, K.D. Essentials of Medical pharmacology,Jaypee Brothers Medical Publishers Ltd, New Delhi, 2008,394-395.
[23]	Sridhar, S.K., Pandeya, S.N., Stables, J.P. and Ramesh, A. “Anticonvulsant activity of hydrazones, Schiff and Mannich bases of isatin derivatives”. Eur J Pharm Sci, 16(3).129-132. Aug.2002.
[24]	Verma, M., Pandeya, S.N., Singh, K.N.and Stables, J.P. “Anticonvulsant activity of Schiff bases of isatin derivatives”. Acta Pharm, 54.49-56. Dec.2004.
[25]	Smitha, S., Pandeya, S.N., Stables, J.P. and Ganapathy, S. “Anticonvulsant and sedative-hypnotic activities of N-Acetyl/Methyl isatin derivatives”.Sci Pharm, 76.621-636. Sept. 2008.