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Vigabatrin increases human brain homocarnosine and improves seizure control
Author(s) -
Petroff Ognen A. C.,
Mattson Richard H.,
Behar Kevin L.,
Hyder Fahmeed,
Rothman Douglas L.
Publication year - 1998
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410440614
Subject(s) - vigabatrin , gabaergic , epilepsy , gamma aminobutyric acid , endocrinology , medicine , chemistry , pharmacology , neuroscience , anticonvulsant , biology , inhibitory postsynaptic potential , receptor
Homocarnosine, a dipeptide of γ‐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 μmol/g) than in other animals. The antiepileptic drug vigabatrin increases human cerebrospinal fluid homocarnosine linearly with daily dose. By using 1 H 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.