Vigabatrin: effect on brain GABA levels measured by nuclear magnetic resonance spectroscopy

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Abstract
Vigabatrin is undoubtedly one of the most exciting anti-epilepsy drugs in use today. Many open and controlled clinical trials have confirmed that it is particularly effective in controlling partial epileptic seizures with or without secondary generalization. Vigabatrin acts to increase GABA levels in the presynaptic nerve terminal by inhibiting the activity of GABA-transaminase. There is no direct correlation between the blood or brain concentration of vigabatrin and its clinical effect, so monitoring vigabatrin levels is not predictive of patient response. However, it is possible to relate the activity of vigabatrin to levels of GABA in the brain, measured by nuclear magnetic resonance spectroscopy (NMRS). NMRS studies show that following administration of vigabatrin, brain concentrations of GABA rise to about 2-3 times their baseline values. This 'extra' GABA is held within the nerve terminal, and is only released during synaptic transmission. Although there appears to be a clear dose-response relationship up to 3 g/day, it is not well documented if higher doses result in proportionately higher brain GABA levels. This finding seems to support the results of clinical studies suggesting that the optimal dose of vigabatrin may be 3 g/day. There is also some evidence for a correlation between the concentration of GABA in the brain and the clinical outcome. Continuing investigations using NMRS aim to confirm these preliminary findings, and to determine the time course and extent of changes in brain GABA levels after vigabatrin administration.