VIGABATRIN - EFFECTS ON HUMAN BRAIN GABA LEVELS BY NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY

Vigabatrin (VGB, Sabril) is a new antiepileptic drug used for treatmen t of partial and secondarily generalized tonic-clonic seizures. Many c ontrolled short- and long-term trials have established efficacy as add -on therapy. Side effects have been infrequent. VGB acts as an irrever sible substrate for gamma-aminobutyric acid (GABA) transaminase that l eads to elevated brain GABA levels. Although this mechanism has been c onfirmed in animals and in cerebrospinal fluid of humans, we report th e first study of brain GABA levels using noninvasive nuclear magnetic resonance spectroscopy. GABA elevation in brain closely parallels VGB dosage and reaches concentrations 2-3 times control values at daily do sage of 3 g. This technique offers promising potential to monitor chan ges induced by VGB as a function of time, dose, and clinical effect.