Anticonvulsant screening of three novel isomeric forms of 4[(dimethylphenyl) amino]-4-oxobut-2-enoic acid in chicks and mice

Abstract

Epilepsy is a disorder of public concern and has been widely treated using various pharmacotherapeutic approaches. Despite many breakthrough in its current management, there is no one drug that is devoid of shortcomings particularly toxicity and cost. Advances in pharmaceutical research have led to the need for a structure guided pharmacologic activity of novel compounds. The aim of this study is to evaluate the anticonvulsant activity of three (3) novel isomeric forms of 4[(dimethylphenyl) amino]-4-oxobut-2-enoic acid in chicks and mice. The 3 isomeric forms i.e. {4-[(2, 4- dimethylphenyl) amino]-4-oxobutenoic acid (A), 4-[(2, 5- dimethylphenyl) amino]-4-oxobutenoic acid (B) and 4-[(2, 6- dimethylphenyl) amino]-4-oxobutenoic acid (C)} were subjected to acute toxicity studies using Lorke’s method of 1983 and anticonvulsant screening using Maximum Electro-Shock Test (MEST) and Pentylenetetrazole test (PTZ). The Median lethal doses (LD50) of compounds A, B, and C were estimated to be 775, 1131, and 1131 mg/kg respectively. In the MEST, compound A (50, 100 and 200 mg/kg) and B (75, 150 and 300 mg/kg) did not show protection at all the doses tested, while compound C (75, 150 and 300 mg/kg) showed a 20% protection across all the doses tested. In the PTZ, compound A, B and C showed no protection. In conclusion, all the 3 isomeric forms of 4[(dimethylphenyl) amino]-4-oxobut-2- enoic acid though possessed some level of protection but not significant against MEST and PTZ models.

Keywords: Anticonvulsant, Epilepsy, Isomers, MEST, PTZ