Oac. Petroff et al., Acute effects of vigabatrin on brain GABA and homocarnosine in patients with complex partial seizures, EPILEPSIA, 40(7), 1999, pp. 958-964
Purpose: 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, ho
mocarnosine and 2-pyrrolidinone.
Methods: In vivo measurements of GABA and homocarnosine were made of a 14-c
c volume in the occipital cortex by using H-1 spectroscopy with a 2.1-Tesla
magnetic resonance spectrometer and an 8-cm surface coil. Six patients (th
ree women) were studied serially during the initiation and maintenance of V
GB as adjunct therapy.
Results: The first, 3 g dose of VGB increased brain GABA by 2.0 mu mol/g wi
thin 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 VG
B given at 48 h was considerably less than that to the first dose, with a m
edian increase of 0.5 mu mol/g within 72 min. After 2-3 months, rechallengi
ng patients taking 1.5-g VGB twice daily with 6 g increased GABA by 0.4 mu
mol/g within 87 min. Homocarnosine increased more gradually than GABA to ab
ove-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. O
nce-a-day dosing is sufficient to increase GABA. Patients may be expected t
o experience the effects of increased homocarnosine within 1 week.