Modulation of pentylenetetrazol-induced seizure activity by branched-chain amino acids and α-ketoisocaproate

Branched-chain amino acids, and mainly leucine act as nitrogen donors in the cerebral glutamate–glutamine cycle, thereby reducing brain excitability. Rats equipped with cortical electrodes received 300 mg/kg of leucine, isoleucine, valine or the ketoacid of leucine, α-ketoisocaproate at 2 h before the induction of seizures by 40 mg/kg pentylenetetrazol. Control groups received saline or a commercial mixture of amino acids, Vamine®. Leucine and isoleucine increased the latency to absence-like and tonic–clonic seizures but did not influence the duration of the tonic–clonic seizure. Vamine®, valine and α-ketoisocaproate had no effect. These data are consistent with the role of leucine in buffering brain glutamate concentration.