Vigabatrin increases human brain homocarnosine and improves seizure control

Homocarnosine, a dipeptide of gamma-aminobutyric acid (GABA) and histidine, is thought to be an inhibitory neuromodulator synthesized in subclasses of GABAergic neurons. Homocarnosine is present in human brain in greater amou nts (0.4-1.0 mu mol/g) than in other animals. The antiepileptic drug vigaba trin increases human cerebrospinal fluid homocarnosine linearly with daily dose. By using H-1 nuclear magnetic resonance spectroscopy, serial occipita l lobe GABA and homocarnosine concentrations were measured in 11 patients s tarted on vigabatrin. Daily low-dose (2 g) vigabatrin increased both homoca rnosine and GABA. Larger doses of vigabatrin (4 g) further increased homoca rnosine but changed GABA levels minimally. Seizure control improved with in creasing homocarnosine and GABA concentrations. Patients whose seizure cont rol improved with the addition of vigabatrin had higher mean homocarnosine, but the same mean GABA concentrations, than those whose seizure control di d not improve. Increased homocarnosine may contribute to improved seizure c ontrol.