Oral administration of fructose-1,6-diphosphate has anticonvulsant activity

Abstract

Recently it has been shown that fructose-1,6-diphosphate (FDP) has dose-dependent anticonvulsant activity in rat models of acute generalized motor seizures induced with chemical convulsants. The present study asked whether FDP also has activity in an epileptic brain after oral administration and activity against non-convulsive seizures. Animals ( n = 14) were administered pilocarpine to induce status epilepticus. Several weeks later, these animals had spontaneous seizures and a baseline rate of seizure frequency was determined over a 6-day period. Animals were then continued without treatment ( n = 8) or 0.5% FDP was added to the drinking water ( n = 6). In animals treated with FDP the seizures completely stopped after 7 days. Removal of FDP from the water resulted in the return of seizure activity in 4 of the 6 animals by 16 days of observation. To induce non-convulsive seizures, animals ( n = 6) received a single injection of γ-butyrolactone (GBL, 100 mg/kg i.p.). All animals had spike-wave activity recorded in the cortex within minutes after GBL administration. Administration of a single injection of FDP (500 g/kg i.p.) had no effect on the baseline cortical activity, nor on the spike-wave activity induced by GBL ( n = 5). These experiments suggest that oral administration of FDP may have utility in the treatment of partial or generalized convulsive seizure disorders, but not absence seizures.