Abstract：
PURPOSE:The antiepileptic drug (AED) vigabatrin (VGB), which exerts its pharmacologic effects on the gamma-aminobutyric acid (GABA) system, causes concentric visual field constriction in >40% of exposed adults. This may be a class effect of all agents with GABA-related mechanisms of action. We compared the concentration-related effects of VGB in rat brain and eye with those of gabapentin (GBP) and topiramate (TPM), both of which have been reported to elevate brain GABA concentrations in humans. METHODS:Adult male rats (n = 10) were administered 0.9% saline (control), VGB (250, 500, 1,000 mg/kg), GBP (50, 100, 200 mg/kg), or TPM (12.5, 25, 50, 100 mg/kg). At 2 h after dosing, animals were killed, a blood sample obtained, the brain dissected into eight distinct regions, and the retina and vitreous humor isolated from each eye. Samples were analyzed for several GABA-related neurochemical parameters, and serum and tissue drug concentrations determined. RESULTS:VGB treatment produced a significant (p < 0.05) dose-related increase in GABA concentrations and decrease in GABA-transaminase activity in all tissues investigated. This effect was most pronounced in the retina, where VGB concentrations were 18.5-fold higher than those in brain. In contrast, GBP and TPM were without effect on any of the neurochemical parameters investigated and did not accumulate appreciably in the retina. CONCLUSIONS:These findings corroborate a previously reported accumulation of VGB in the retina, which may be responsible for the visual field constriction observed clinically. This phenomenon does not appear to extend to other GABAergic drugs, suggesting that these agents might not cause visual field defects.
journal_name
Epilepsiajournal_title
Epilepsiaauthors
Sills GJ,Butler E,Forrest G,Ratnaraj N,Patsalos PN,Brodie MJdoi
10.1046/j.1528-1157.2003.04203.xsubject
Has Abstractpub_date
2003-07-01 00:00:00pages
886-92issue
7eissn
0013-9580issn
1528-1167pii
04203journal_volume
44pub_type
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