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Acute Effects of Vigabatrin on Brain GABA and Homocarnosine in Patients with Complex Partial Seizures
Author(s) -
Petroff Ognen A. C.,
Hyder Fahmeed,
Collins Theresa,
Mattson Richard H.,
Rothman Douglas L.
Publication year - 1999
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1999.tb00803.x
Subject(s) - vigabatrin , neuroscience , complex partial seizures , partial seizures , epilepsy , partial epilepsy , medicine , anticonvulsant , psychology , anesthesia , temporal lobe
Summary:Purpose: The acute, subacute, and chronic effects of vigabatrin (VGB) were studied in patients with refractory complex partial seizures. VGB increases human brain γ‐aminobutyric acid (GABA) and the related metabolites, homocarnosine and 2‐pyrrolidinone. Methods: 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. Six patients (three women) were studied serially during the initiation and maintenance of VGB as adjunct therapy. Results: The first, 3 g dose of VGB increased brain GABA by 2.0 μmol/g within 81 min of oral administration. After 2 h, median edited GABA remained essentially the same for 2 days. The response to the second, 3‐g dose of VGB given at 48 h was considerably less than that to the first dose, with a median increase of 0.5 μmol/g within 72 min. After 2–3 months, rechallenging patients taking 1.5‐g VGB twice daily with 6 g increased GABA by 0.4 μmol/g within 87 min. Homocarnosine increased more gradually than GABA to above‐normal levels after a week of VGB therapy. Conclusions: VGB promptly elevates brain GABA and presumably offers partial protection against further seizures within hours of the first oral dose. Once‐a‐day dosing is sufficient to increase GABA. Patients may be expected to experience the effects of increased homocarnosine within 1 week.