title: Topiramate rapidly raises brain GABA in epilepsy patients.
abstract: OBJECTIVE
  The short- and long-term pharmacodynamic effects of topiramate (TPM) on brain gammay-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 > or =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.
authors: Department of Neurology, Yale University, New Haven, Connecticut 06520-8018, USA.
authors: O A
authors: OA
authors: Petroff
authors: F
authors: F
authors: Hyder
authors: D L
authors: DL
authors: Rothman
authors: R H
authors: RH
authors: Mattson
mesh_terms: D000284:Administration, Oral; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001923:Brain Chemistry / Q000187:drug effects*; D002336:Carnosine / Q000031:analogs & derivatives / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D017029:Epilepsy, Complex Partial / Q000188:drug therapy*; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D009682:Magnetic Resonance Spectroscopy / Q000706:statistics & numerical data; D009778:Occipital Lobe / Q000737:chemistry / Q000187:drug effects; D011760:Pyrrolidinones / Q000032:analysis; D013268:Stimulation, Chemical; D000077236:Topiramate; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
chemical_list: D000927:Anticonvulsants; D011760:Pyrrolidinones; D000077236:Topiramate; D005632:Fructose; C005038:homocarnosine; D005680:gamma-Aminobutyric Acid; D002336:Carnosine