MAGNESIUM IS MORE EFFICACIOUS THAN PHENYTOIN IN REDUCING N-METHYL-D-ASPARTATE SEIZURES IN RATS

OBJECTIVE: Although magnesium sulfate is one of the most commonly used agents for seizure prophylaxis in preeclampsia, its efficacy relative to other anticonvulsants is incompletely investigated. The underlying mechanisms of eclamptic seizures are unknown, and there is currently no universally accepted animal model for eclampsia. However, one commo nly used method for studying the relative efficacy of antiepileptic dr ugs is through their effect on N-methyl-D-aspartate-induced seizures. Our aim was to compare the anticonvulsant effects of phenytoin and mag nesium sulfate in an N-methyl-D-aspartate-induced seizure model.STUDY DESIGN: Twenty-one female rats were each stereotaxically implanted wit h a chronic indwelling bipolar recording electrode in the hippocampus and an injection cannula in the lateral cerebral ventricle. After 7 da ys animals were randomly given 90 mg/kg magnesium sulfate (n = 7), 50 mg/kg phenytoin, or saline solution (n = 7) intravenously. Fifteen min utes after the infusions animals were given 20 mu g/mu l N-methyl-D-as partate by direct intraventricular injection, and seizure activity was assessed for 20 minutes thereafter. All data were analyzed with the M ann-Whitney test. RESULTS: When compared with saline solution controls , total duration of seizure activity in animals treated with magnesium sulfate was significantly decreased (p < 0.05) and time to onset of s eizure activity was significantly increased (p < 0.05). However, rats that received phenytoin did not show significant changes in these para meters. The post-N-methyl-D-aspartate seizure mortality rate was 50% i n the saline solution controls and 29% in the phenytoin group, whereas none of the rats that received magnesium sulfate died. CONCLUSION: Th ese results suggest that magnesium sulfate is a significantly more eff ective prophylactic agent than phenytoin for N-methyl-D-aspartate-indu ced seizures.