ANTICONVULSANT ACTIVITY OF ISONICOTINIC ACID HYDRAZONE DERIVATIVES USING MES, scPTZ AND ROTOROD NEUROTOXICITY MODELS

Abstract

Epilepsy is a chronic neurological disorder, involving group of nerve cells, or neurons, in the brain. Many classes of antiepileptic
drugs are being prescribed and used by the stake holders but most of them are associated with serious side effects and toxicity. There is a strong
need of new antiepileptic molecules with less side effects and toxicity. Objective: A series of aryl acid hydrazones of Isonicotinic acid hydrazide
(RINH1 -RINH14) were synthesized and evaluated for Anticonvulsant activity. Material and Method: Compounds (RINH1 -RINH14) were
synthesized by refluxing Isonicotinic acid hydrazide with different substituted benzaldehydes/ substituted acetophenones in absolute ethanol.
Melting points of all synthesized compounds were monitored by open glass-capillary tube method on Digital Melting point apparatus and are
uncorrected. The synthesized compounds were tested for anticonvulsant potential using MES and scPTZ whereas neurotoxicity was determined
using Rotarod model. Result and Discussion: At 100mg/kg compound RINH10 have shown 29% protection at both 0.5hr and 4.0 time interval
.At 300mg/kg and 0.5 hr, compounds RINH4 and RINH10 showed 100% and 50 % protection respectively. Compounds RINH4 and RINH10 have
better anti MES activity proving that halogens have prominent contribution in Anticonvulsant activity. In scPTZ screen, all synthesized Acid
hydrazone (RINH1- RINH14 ) did not show any protection at 30, 100,300 mg/kg , at 0.5 hr and 4.0 hr duration .In rotorod test i.e neurotoxicity
screen, compound RINH5, RINH6 , RINH10 have shown toxicity. Conclusion: The synthesized new molecules were proved to be having
anticonvulsant activity with less signs of neurotoxicity.