Topiramate rapidly raises brain GABA in epilepsy patients

Purpose: The short- and long-term pharmacodynamic effects of topiramate (TP M) on brain gamma -aminobutyric acid (GABA) metabolism were studied in pati ents with complex partial seizures. Methods: In vivo measurements of GABA, homocarnosine, and pyrrolidinone wer e made of a 14-cc volume in the occipital cortex using H-1 spectroscopy wit h a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Fif teen patients (four men) were studied serially after the first, oral dose ( 100 mg) of TPM. Results: The first dose of TPM increased brain GABA within 1 h. Within 4 h, GABA was increased by 0.9 mM (95% CI, 0.7-1.1). Brain GABA remained elevat ed for greater than or equal to 24 h. Pyrrolidinone and homocarnosine incre ased slowly during the first day. Daily TPM therapy (median, 300 mg; range, 200-500) increased GABA (0.3 mM; 95% CI, 0.1-0.5), homocarnosine (0.4 mM; 95% CI, 0.3-0.5). and pyrrolidinone (0.15 mM; 95% CI, 0.10-0.19), compared with levels before TPM. There was no dose response evident with daily TPM d oses of 200-500 mg. Conclusions: TPM promptly elevates brain GABA and presumably offers partial protection against further seizures within hours of the first oral dose. P atients may expect to experience the effects of increased homocarnosine and pyrrolidinone within 23 h.