Metformin prevents phenytoin induced cognitive impairment

Cognitive impairment is one of the major problems associated with antiepileptic drugs. Phenytoin is one of the widely used anticonvulsant drugs, but it adversely affects learning and memory on prolonged use due to generation of reactive oxygen species. Metformin promotes neurogenesis, enhances spatial memory function and protects the brain against oxidative imbalance. Metformin, due to its interference with apoptotic cascade, prevents cell death. Hence the present study was undertaken to evaluate the nootropic effects of metformin against phenytoin induced cognitive impairment by using several preclinical models such as actophotometer, rotarod, elevated plus maze, radial arm maze and Y-maze. Adult wistar albino rats (150-200g) of both sexes were divided into three groups. Group-I was treated as control, Group-II was administered with phenytoin whereas Group-III was subjected to metformin followed by phenytoin. Metformin (200mg/kg) was administered orally 1h before administration of phenytoin (25mg/kg) for 21 days. Metformin showed significant (p<0.05) increase in locomotor activity in actophotometer, time of fall in rotarod, number of correct entries in radial arm maze, % SAB in Y-maze and decrease in time spent in open arm in elevated plus maze, thereby reversing the effects of phenytoin.