Visual field constriction: accumulation of vigabatrin but not tiagabine in the retina

Sills, G.J., Patsalos, P.N., Butler, E., Forrest, G., Ratnaraj, N. and Brodie, M.J. (2001) Visual field constriction: accumulation of vigabatrin but not tiagabine in the retina. Neurology, 57(2), pp. 196-200. (doi:10.1212/WNL.57.2.196) (PMID:11468302)

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Abstract

Background: The antiepileptic drug (AED) vigabatrin (VGB) causes concentric visual field constriction. Anecdotal reports involving tiagabine (TGB) have implied that this may be a class effect of all AEDs with γ-aminobutyric acid (GABA)–related actions. We investigated the pharmacokinetic and pharmacodynamic profiles of VGB and TGB in rat brain and eye. Methods: Adult male rats (n = 8) were administered 0.9% saline (control), VGB (500 or 1,000 mg/kg), or TGB (5, 10, or 20 mg/kg). At 1 (TGB) and 4 hours (VGB) postdosing, the animals were killed, a blood sample was obtained, their brains were dissected into five anatomic regions, and the retina and vitreous humor were isolated from each eye. Samples were analyzed for GABA concentrations and the activity of the enzyme GABA-transaminase (GABA-T). Plasma and tissue drug concentrations were also determined. Results: VGB treatment produced a decrease in the activity of GABA-T and a rise in GABA concentrations in all tissues investigated. This effect was most pronounced in the retina. VGB concentrations were as much as fivefold higher in the retina than in the brain. TGB was without effect on GABA concentrations and activity of GABA-T. TGB concentrations were notably lower in the retina than in the brain. Conclusions: Accumulation of VGB in the retina, with or without an increase in GABA, may be responsible for the visual field constriction reported clinically. In contrast, TGB had no effect on GABA concentrations and did not accumulate in the retina. These results suggest that TGB is unlikely to cause visual field defects in humans.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Brodie, Professor Martin and Butler, Mrs Elaine and Forrest, Mr Gerard and Sills, Dr Graeme
Authors: Sills, G.J., Patsalos, P.N., Butler, E., Forrest, G., Ratnaraj, N., and Brodie, M.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Neurology
Publisher:American Academy of Neurology
ISSN:0028-3878
ISSN (Online):1526-632X

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