Modulation of pentylenetetrazol-induced seizure activity by branched-chainamino acids and alpha-ketoisocaproate

Branched-chain amino acids, and mainly leucine act as nitrogen donors in th e cerebral glutamate-glutamine cycle, thereby reducing brain excitability. Rats equipped with cortical electrodes received 300 mg/kg of leucine, isole ucine, valine or the ketoacid of leucine, alpha-ketoisocaproate at 2 h befo re the induction of seizures by 40 mg/kg pentylenetetrazol. Control groups received saline or a commercial mixture of amino acids, Vamine(R). Leucine and isoleucine increased the latency to absence-like and tonic-clonic seizu res but did not influence the duration of the tonic-clonic seizure. Vamine( R). valine and a-ketoisocaproate had no effect. These data are consistent w ith the role of leucine in buffering brain glutamate concentration. (C) 199 9 Elsevier Science B.V. All rights reserved.