Metabolic influence of gabapentin in brain

De novo synthesis of glutamate in excised rat retinas results in incorporation of 14 CO 2 into neuronal glutamate that is partially (30%) inhibited by the neuroactive drug gabapentin (Lieth et al . 2001). Gabapentin inhibits the cytosolic form of branched chain aminotransferase (BCATc) and prevents formation of glutamate via transamination of α‐ketoglutarate by branched chain aminoacids. The present study was an evaluation of the influence of gabapentin on glutamate synthesis in the whole brain in vivo . Gabapentin or vehicle was given IP (100 mg/kg) 30 min prior to the experiment. The rats were continuously infused through the jugular vein with H 14 CO 3 (1.0 mCi/h) and U 13 C‐glucose (1 m m ) while blood samples were taken from the carotid artery. Blood H 14 CO 3 specific activity and U 13 C glucose concentration remained constant throughout infusions and rats were sacrificed at 5, 10, 20, 40 and 60 min Heads were quick frozen in liquid nitrogen and frozen brains removed and extracted with perchloric acid. 14 C‐metabolites were separated chromatographically and assayed as described previously. The 13 C data are currently being analyzed to determine 13 C‐glutamate turnover. The 14 C‐glutamate specific activity increased with a half‐life of 6 ± 1 min in control rats and 9 ± min in gabapentin treated rats. At steady state, the H 14 CO 3 in the control glutamate pool was 8.90 ± 0.3 and 7.92 ± 0.6 nmoles/mg protein in the gabapentin pool. The corresponding values in the glutamine pools were 9.48 ± 0.4 and 7.73 ± 0.6 nmoles/mg protein. The data suggest that gabapentin also inhibits de novo synthesis of glutamate in the whole brain but less so than in the intact excised retina. Nevertheless, gabapentin may induce larger changes in brain areas with high concentrations of glutamatergic neurons.