Taurine supplementation to anti-seizure drugs as the promising approach to treat pharmacoresistant epilepsy: A pre-clinical study

Background Pharmacoresistance leads to severe, irreversible disabilities and premature death in ∼30% cases of epilepsy despite adequate and appropriate treatment with available anti-seizure drugs (ASDs) without any underlying cause. In light of the large body of evidence which suggests the anti-seizure action of taurine in experimental animals and its wide safety margins in human, supplementation of this inhibitory amino-sulfonic acid to available ASDs seems promising to treat pharmacoresistant epilepsy. Methods We examined the anti-seizure effect of lamotrigine (15 mg/kg), levetiracetam (40 mg/kg), carbamazepine (40 mg/kg), phenytoin (35 mg/kg) & taurine (50, 100 & 200 mg/kg) in lamotrigine pre-treated pentylenetetrazole-kindled mice (LPK) which mimic core features of pharmacoresistant epilepsy, either alone ASDs or in combinations whereby three different doses of taurine were supplemented with tested ASDs. Results Both, the ASDs and the taurine were failed to suppress generalized tonic-clonic seizures in LPK mice. However, taurine supplementation clearly restored the anti-seizure effect of tested ASDs. Further neurochemical studies revealed that higher levels of taurine in the hippocampus and cerebral cortex restored the imbalance between major excitatory neurotransmitters glutamate & its inhibitory counterpart GABA. Conclusions These findings emphasize that supplementation of taurine with ASDs may be useful to treat pharmacoresistant epilepsy. Thus, further clinical validation is encouraged.