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

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.

Evaluation of Antiepileptic Activity of Methanolic Extract of Opuntia Ficus Indica Flower in Mice

“…This results in neuronal excitotoxicity leading to seizures and convulsions characterized by clonic and tonic phases. [29] so the NMDA receptor antagonist ketamine, diazocilpine have reported the effect against PTZ induced seizure.…”

Recent Developments of Hydrazide/Hydrazone Derivatives and Their Analogs as Anticonvulsant Agents in Animal Models

“…Eggadi et al [] evaluated the isatin‐3‐[ N 2 ‐(2‐benzalaminothiazol‐4‐yl)] hydrazones for antiepileptic effect in both MES‐ and PTZ‐induced convulsion models. In animals, isatin derivatives 3a , 3b , 3c , and 3d restored brain GABA levels a mesure of their antiepileptic activity.…”

“…Considering the structural-activity relationships for this class of compounds and analyzing the contribution of different groups at C-3 position to the anticonvulsant efficacy the authors suggested that both the size and the nature of the substituents modulated activity. Eggadi et al [2013] evaluated the isatin-3-[N 2 -(2-benzalaminothiazol-4-yl)] hydrazones for antiepileptic effect in both MES-and PTZ-induced convulsion models. In animals, isatin derivatives 3a, 3b, 3c, and 3d restored brain GABA levels a mesure of their antiepileptic activity.…”

5-Chloro-1-methylindoline-2,3-dione

“…5-Chloro-1H-indole-2,3-dione is a derivative of isatin (1H-Indole-2,3-dione) which has several interesting activities such as anti-tubercular (Aboul-Fadl et al, 2010), cytotoxicity (Subba Reddy et al, 2012) anti-inflammatory, (Anisetti et al; anti-convulsant (Eggadi et al, 2013) anxiolytic (Silva et al, 2013) and anti-depressant (Radhika et al, 2012).…”