Acute effects of vigabatrin on brain GABA and homocarnosine in patients with complex partial seizures.
OBJECTIVE
The acute, subacute, and chronic effects of vigabatrin (VGB) were studied in patients with refractory complex partial seizures. VGB increases human brain gamma-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 1H 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 micromol/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 micromol/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 micromol/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.
Department of Neurology, Yale University, New Haven, Connecticut 06520-8018, USA.
O A
OA
Petroff
F
F
Hyder
T
T
Collins
R H
RH
Mattson
D L
DL
Rothman
D000284:Administration, Oral; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D002336:Carnosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D017029:Epilepsy, Complex Partial / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009778:Occipital Lobe / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
D000927:Anticonvulsants; C005038:homocarnosine; D005680:gamma-Aminobutyric Acid; D002336:Carnosine; D020888:Vigabatrin