The effect of aspartame on seizure susceptibility and the anticonvulsant action of ethosuximide, valproate and phenytoin in mice

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Aspartame (APM) when given as a single (1 g/kg, orally) or repeated (100 mg/kg, orally for 14 days) neither affected the spontaneous locomotor activity of mice in an open field, nor altered pentylenetetrazol (PTZ)-induced seizure threshold. Subacute, but not acute, APM administration was found to decrease the anticonvulsant activity of ethosuximide (ETH) and valproate (VPA) in PTZ-induced seizure threshold, and of phenytoin (PHT) in PTZ-induced generalized tonic clonic seizures. The antagonism of the anticonvulsant activity of ETH, VPA and PHT was not due to alterations of plasma levels or pharmacokinetics of the antiepileptic drugs, but could be due to an increase of brain excitatory and/or decrease of brain inhibitory neurotransmitters. Subacute APM administration was found to decrease brain adrenaline and noradrenaline levels which might increase seizure susceptibility in mice. VPA and PHT, but not ETH, were found to antagonize subacute APM-induced decrease in brain adrenaline level. On the other hand, subacute APM administration was found to partially antagonize VPA induced decrease in brain aspartate and increase in GABA levels; and PHT-induced decrease in brain glutamate and increase in GABA levels. The results of the present study showed that repeated oral low dose aspartame administration may not be proconvulsant in mice, but antagonize the anticonvulsant activity of the antiepileptic drugs ethosuximide, valproate and phenytoin.

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