topiramate and homocarnosine

To assess the relation between seizure control and brain homocarnosine and gamma-aminobutyric acid (GABA) levels of patients with complex partial seizures taking gabapentin (GBP) or topiramate (TPM) as adjunctive therapy.. In vivo measurements of GABA and homocarnosine were made of a 14-cc volume in the occipital cortex by using (1)H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Poor seizure control was defined as more recent seizures than the median for the two groups of patients studied.. Homocarnosine levels were higher in patients with better seizure control than in those with poor control. No differences were found in the intracellular GABA levels between the patients who responded to GBP or TPM compared with those who did not.. In the visual neocortex, which is remote from the presumed seizure-onset zone, higher homocarnosine levels were associated with better seizure control in the patients taking GBP or TPM as adjunctive therapy; elevated intracellular GABA levels appeared to offer no additional protection.

Topics: Adult; Amines; Anticonvulsants; Brain Chemistry; Carnosine; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Epilepsy, Complex Partial; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neocortex; Topiramate; Treatment Outcome; Visual Cortex

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.. 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.. 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.. 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.

Topics: Administration, Oral; Anticonvulsants; Brain Chemistry; Carnosine; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsy, Complex Partial; Fructose; gamma-Aminobutyric Acid; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Occipital Lobe; Pyrrolidinones; Stimulation, Chemical; Topiramate

To measure the effects of topiramate on brain gamma-aminobutyric acid (GABA) in patients with epilepsy.. Topiramate is a new antiepileptic medication with multiple putative mechanisms of action. In a recent meta-analysis of the newer antiepileptic drugs, topiramate was the most potent. Homocarnosine and pyrrolidinone are important metabolites of GABA with antiepileptic actions.. In vivo measurements of GABA, homocarnosine, and pyrrolidinone were made of a 14-cm3 volume in the occipital cortex using 1H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Twelve patients (eight women) with refractory complex partial seizures were studied while using topiramate. Nine epilepsy-free, drug-free volunteers served as control subjects.. Topiramate increased mean brain GABA, homocarnosine, and pyrrolidinone concentrations in all patients. In paired measurements, brain GABA increased by 0.7 micromol/g (SD 0.3, n 7, 95% CI 0.4 to 1.0, p < 0.01). Homocarnosine increased by 0.5 micromol/g (SD 0.2, n 7, 95% CI 0.3 to 0.7, p < 0.001). Pyrrolidinone increased by 0.21 micromol/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.. Topiramate increased brain GABA, homocarnosine, and pyrrolidinone to levels that could contribute to its potent antiepileptic action in patients with complex partial seizures.

Topics: Adolescent; Adult; Anticonvulsants; Brain; Carnosine; Epilepsy; Female; Fructose; gamma-Aminobutyric Acid; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Pyrrolidinones; Topiramate