title: Vigabatrin increases human brain homocarnosine and improves seizure control.
abstract: Homocarnosine, a dipeptide of gamma-aminobutyric acid (GABA) and histidine, is thought to be an inhibitory neuromodulator synthesized in subclasses of GABAergic neurons. Homocarnosine is present in human brain in greater amounts (0.4-1.0 micromol/g) than in other animals. The antiepileptic drug vigabatrin increases human cerebrospinal fluid homocarnosine linearly with daily dose. By using 1H nuclear magnetic resonance spectroscopy, serial occipital lobe GABA and homocarnosine concentrations were measured in 11 patients started on vigabatrin. Daily low-dose (2 g) vigabatrin increased both homocarnosine and GABA. Larger doses of vigabatrin (4 g) further increased homocarnosine but changed GABA levels minimally. Seizure control improved with increasing homocarnosine and GABA concentrations. Patients whose seizure control improved with the addition of vigabatrin had higher mean homocarnosine, but the same mean GABA concentrations, than those whose seizure control did not improve. Increased homocarnosine may contribute to improved seizure control.
authors.affiliation: Department of Neurology, Yale University, New Haven, CT 06520-8018, USA.
authors.forename: O A
authors.initials: OA
authors.lastname: Petroff
authors.forename: R H
authors.initials: RH
authors.lastname: Mattson
authors.forename: K L
authors.initials: KL
authors.lastname: Behar
authors.forename: F
authors.initials: F
authors.lastname: Hyder
authors.forename: D L
authors.initials: DL
authors.lastname: Rothman
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D002336:Carnosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017029:Epilepsy, Complex Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009778:Occipital Lobe / Q000378:metabolism*; D009994:Osmolar Concentration; D016896:Treatment Outcome; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; C005038:homocarnosine; D005680:gamma-Aminobutyric Acid; D002336:Carnosine; D020888:Vigabatrin