Topiramate increases brain GABA, homocarnosine, and pyrrolidinone in patients with epilepsy

Objective: To measure the effects of topiramate on brain gamma-aminobutyric acid (GABA) in patients with epilepsy. Background: Topiramate is a new ant iepileptic medication with multiple putative mechanisms of action. In a rec ent meta-analysis of the newer antiepileptic drugs, topiramate was the most potent. Homocarnosine and pyrrolidinone are important metabolites of GABA with antiepileptic actions. Methods: In vivo measurements of GABA, homocarn osine, and pyrrolidinone were made of a 14-cm(3) volume in the occipital co rtex using IH spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Twelve patients (eight women) with refractory co mplex partial seizures were studied while using topiramate. Nine epilepsy-f ree, drug-free volunteers served as control subjects. Results: Topiramate i ncreased mean brain GABA, homocarnosine, and pyrrolidinone concentrations i n all patients. In paired measurements, brain GABA increased by 0.7 mu mol/ g (SD 0.3, n 7, 95% CI 0.4 to 1.0, p < 0.01). Homocarnosine increased by 0. 5 mu mol/g (SD 0.2, n 7, 95% CI 0.3 to 0.7,p < 0.001). Pyrrolidinone increa sed by 0.21 mu mol/g (SD 0.06, n 7, 95% CI 0.16 to 0.27, p < 0.01). In two additional patients, GABA, homocarnosine, and pyrrolidinone increased after they were switched from vigabatrin to topiramate. Conclusions: Topiramate increased brain GABA, homocarnosine, and pyrrolidinone to levels that could contribute to its potent antiepileptic action in patients with complex par tial seizures.