Visual electrophysiological effect of a GABA transaminase blocker.
Vigabatrin is an antiepileptic drug for the treatment of partial seizures. The anticonvulsant effect is achieved by irreversible inhibition of the enzyme GABA-transaminase which catalyses the inactivation of GABA. Vigabatrin has been associated with visual field loss and electrophysiological abnormalities. The purpose of the study was to determine any alterations in normal volunteers of the visual field and the visual electrophysiology resulting from a short exposure to vigabatrin. A three-way, double-blind study of placebo, carbamazepine and vigabatrin was undertaken at baseline and on days two, four and nine. Seven subjects completed all three cycles and 14 subjects (six females and eight males; mean age 27.3 years SD 6.7) completed at least one cycle. Static threshold automated perimetry comprised Humphrey Visual Field Analyzer Programs 30-2 and 30/60-2. Electro-oculography and electroretinograms were performed with undilated pupils using the Medelec Ganzfeld stimulator GS2000. The visual field was unaffected by placebo, carbamazepine or vigabatrin. The group mean amplitudes and latencies for the scotopic ERG, 30 Hz flicker ERG and the oscillatory potentials remained unchanged for any cycle. The group mean photopic ERG b-wave latency increased from baseline (p<0.05); no significant change occurred with carbamazepine or placebo. The group mean Arden Index for vigabatrin decreased from baseline to day 9 (p<0.01); no significant differences were present for carbamazepine or placebo. Vigabatrin has a rapid effect on both the photopic ERG and the EOG; however, the changes merely reflect alterations in retinal GABA levels secondary to concomitant blocking of GABA transaminase by existing vigabatrin therapy.
Harding
G F
GF
Clinical Neurophysiology Unit, Psychology Institute Aston University, Aston Triangle, Birmingham, UK.
Robertson
K A
KA
Edson
A S
AS
Barnes
P
P
Wild
J
J
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology; D002220:Carbamazepine / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D004585:Electrooculography / Q000187:drug effects*; D004596:Electroretinography / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D020888:Vigabatrin / Q000494:pharmacology; D014794:Visual Fields / Q000187:drug effects*
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D002220:Carbamazepine; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin