Topiramate Rapidly Raises Brain GABA in Epilepsy Patients
Article first published online: 20 DEC 2001
Volume 42, Issue 4, pages 543–548, April 2001
How to Cite
Petroff, O. A. C., Hyder, F., Rothman, D. L. and Mattson, R. H. (2001), Topiramate Rapidly Raises Brain GABA in Epilepsy Patients. Epilepsia, 42: 543–548. doi: 10.1046/j.1528-1157.2001.18800.x
- Issue published online: 20 DEC 2001
- Article first published online: 20 DEC 2001
- Accepted December 13, 2000.
- γ-Aminobutyric acid;
- 1H nuclear magnetic resonance spectroscopy;
- Antiepileptic drugs
Summary: Purpose: The short- and long-term pharmacodynamic effects of topiramate (TPM) on brain γ-aminobutyric acid (GABA) metabolism were studied in patients with complex partial seizures.
Methods: In vivo measurements of GABA, homocarnosine, and pyrrolidinone were made of a 14-cc volume in the occipital cortex using 1H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Fifteen 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 elevated for ≥24 h. Pyrrolidinone and homocarnosine increased 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 doses 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. Patients may expect to experience the effects of increased homocarnosine and pyrrolidinone within 24 h.