Visual field constriction

Sills, Graeme J.; Patsalos, Philip N.; Butler, Elaine; Forrest, Gerard; Ratnaraj, Neville; Brodie, Martin J.

doi:10.1212/wnl.57.2.196

Cited by 66 publications

(55 citation statements)

References 41 publications

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“…Although another study found no retinal lesions after administering VGB orally for 1 year to CD[SD]BR (albino) rats, this study also hypothesized that light has a critical role in VGB retinotoxicity (28). Finally, because GABA can be toxic to neurons (29,30), VGB retinotoxicity may stem from higher retinal GABA levels (25,26).…”

mentioning

confidence: 70%

“…We used 500 µM VGB as a test concentration because it is in the range needed to obtain electrophysiologic effects in hippocampal slices (31) and is well below the ≥1 mM concentrations achieved in the retina 2 to 4 h after Sprague-Dawley rats receive an intraperitoneal injection of 1,000 mg/kg VGB (25,26). By light microscopy, isolated retinas incubated with ≤500 µM VGB for 20 h in the dark showed no histologic change (Fig.…”

Section: Ex Vivo Experimentsmentioning

confidence: 99%

“…We selected this VGB dose because it results in high VGB levels, significant decreases in GABA transaminase activity, and significant increases in GABA levels in the retinas of Sprague-Dawley rats (25,26). Rats exposed to the standard light cycle after receiving VGB were less active than the saline controls.…”

Section: In Vivo Experimentsmentioning

confidence: 99%

“…The ex vivo preparation provides better control over experimental variables, whereas the in vivo studies allow extrapolation to an intact system (24). We investigated whether VGB produces acute retinotoxicity because retinal VGB and GABA levels increase 2 to 4 h after intraperitoneal injections of VGB in Sprague-Dawley rats (25,26). We examined the role of light because oral administration of VGB for 90 days produced disorganization of the outer nuclear layer of the retinas in Sprague-Dawley (albino) but not in Lister-Hooded (pigmented) rats (27).…”

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confidence: 99%

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Acute Vigabatrin Retinotoxicity in Albino Rats Depends on Light But Not GABA

Izumi¹,

Ishikawa

Benz³

et al. 2004

Epilepsia

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Summary:Purpose: Vigabatrin (VGB) is an irreversible inhibitor of γ -aminobutyric acid (GABA) transaminase. Its use as an antiepileptic drug (AED) has been limited because it causes retinal dysfunction, leading to visual field defects (VFDs). We performed this study to identify factors contributing to acute VGB retinotoxicity.Methods: In ex vivo experiments, Sprague-Dawley rat retinas were isolated and incubated with VGB or GABA in the presence or absence of light. In in vivo experiments, Sprague-Dawley rats were given intraperitoneal injections of VGB and then exposed to light or kept in the dark. The retinas were analyzed histologically by using both light and electron microscopy.Results: Incubating retinas with 50-500 µM VGB under 20,000 Lux white light for ≤20 h caused a characteristic time-and dose-dependent degeneration limited to the outer retina. Incubating retinas with 500 µM VGB in darkness for 20 h caused no damage. Five hundred micromolar GABA and 50 µM tiagabine were not toxic in the presence or absence of light. Sprague-Dawley rats exposed to an intense white light for 20 h after a 1,000-mg/kg intraperitoneal injection of VGB showed damage in the outer retina, whereas those kept in the dark did not.Conclusions: Direct exposure of the retina to VGB causes acute retinotoxicity that depends on light exposure rather than GABA accumulation.

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mentioning

confidence: 70%

Section: Ex Vivo Experimentsmentioning

confidence: 99%

Section: In Vivo Experimentsmentioning

confidence: 99%

mentioning

confidence: 99%

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Acute Vigabatrin Retinotoxicity in Albino Rats Depends on Light But Not GABA

Izumi¹,

Ishikawa

Benz³

et al. 2004

Epilepsia

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“…The clinical application of VGB has been drastically limited after the observation that the drug irreversibly restricts the peripheral visual field in patients receiving VGB (Lawden et al, 1999;Wild et al, 1999). Experimental studies on rats have indicated that VGB preferentially accumulated in the retina reaching concentrations five-fold higher than in the brain, which was additionally associated with a threefold increase in GABA levels in the retina (Sills et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological and Behavioral Characteristics of Interactions between Vigabatrin and Conventional Antiepileptic Drugs in Pentylenetetrazole-Induced Seizures in Mice: An Isobolographic Analysis

Łuszczki

Wojcik-Cwikla

Andres

et al. 2004

Neuropsychopharmacol

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To characterize the anticonvulsant effects and types of interactions exerted by mixtures of vigabatrin (VGB) and conventional antiepileptic drugs (valproate (VPA), ethosuximide (ESM), phenobarbital (PB), and clonazepam (CZP)) in pentylenetetrazole (PTZ)-induced seizures in mice, the isobolographic analysis for three fixed-ratio combinations of 1 : 3, 1 : 1, and 3 : 1 was used. The adverse-effect profile of the combinations tested, at the doses corresponding to their median effective doses (ED 50 ) at the fixed-ratio of 1 : 1 against PTZ-induced seizures, was determined by the chimney (motor performance), step-through passive avoidance (long-term memory), pain threshold (pain sensitivity), and Y-maze (general explorative locomotor activity) tests in mice. Additionally, the observed isobolographic interactions were verified in terms of a pharmacokinetic interaction existence. VGB combined with PB or ESM exerted supra-additive (synergistic) interactions against the clonic phase of PTZ-induced seizures, which was associated with the increment of PB or ESM concentrations in the brains of examined animals. The remaining combinations tested (ie VGB þ VPA and VGB þ CZP) occurred additive in the PTZ test, which was associated with no significant changes in the brain concentrations of VPA and CZP. None of the examined combinations exerted motor impairment in the chimney test in mice. In the standard variant of passive avoidance task (current of 0.6 mA; 2 s of stimulus duration), the combinations of VGB þ CZP and VGB þ VPA significantly affected long-term memory in mice. Moreover, VGB in a dose-dependent manner lengthened the latency to the first pain reaction in the pain threshold test in mice. The modified variant of step-through passive avoidance task (current of 0.6 mA; stimulus duration based on the latency from the pain threshold test) revealed no significant changes in the long-term memory of animals for the combinations of VGB þ VPA and VGB þ CZP; so the observed effects in the standard variant of passive avoidance task were a result of the antinociceptive effects produced by VGB. In the Y-maze test, VGB also, in a dose-dependent manner, increased the general explorative locomotor activity of the animals tested. Similarly, the total number of arm entries in the Y-maze was significantly increased for the combinations of VGB þ CZP and VGB þ ESM, but not for VGB þ PB and VGB þ VPA. The application of VGB in combination with PB, ESM, CZP, and VPA suppressed the clonic phase of PTZ-induced seizures, having no harmful or deleterious effects on behavioral functioning of the animals tested, which might be advantageous in further clinical practice.

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Drug Toxicity in Neonates, Infants and Young Children

Choonara

2009

General, Applied and Systems Toxicology

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Neonates, infants and young children may experience the same drug toxicity as adults. They may also experience specific drug toxicity that adults do not experience. This may be associated with toxicity related to growth and development, for example the adverse effect of corticosteroids on growth or development of the brain following exposure in the early period of neonatal life. Alternatively they may develop a specific toxicity in relation to a condition that does not occur in adults, for example Reye's syndrome following exposure to salicylates during the presence of a viral infection. The altered drug metabolism within paediatric patients is an additional risk factor for drug toxicity. This is most marked in the neonatal period and is illustrated by the impaired metabolism of chloramphenicol which results in cardiovascular collapse. Similarly, the altered metabolism of antiepileptic drugs such as sodium valproate in children less than two years of age predisposes this particular age group to hepatotoxicity. Other specific examples of drug toxicity in paediatric patients are given in this chapter and these include examples of percutaneous and excipient toxicity.

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Visual field constriction

Cited by 66 publications

References 41 publications

Acute Vigabatrin Retinotoxicity in Albino Rats Depends on Light But Not GABA

Acute Vigabatrin Retinotoxicity in Albino Rats Depends on Light But Not GABA

Pharmacological and Behavioral Characteristics of Interactions between Vigabatrin and Conventional Antiepileptic Drugs in Pentylenetetrazole-Induced Seizures in Mice: An Isobolographic Analysis

Drug Toxicity in Neonates, Infants and Young Children

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