Search PubMed⌕ Search

PubMed · 11470707

Vigabatrin effect on inner retinal function.

Abstract

OBJECTIVE: To determine the degree of electroretinal dysfunction in a group of patients taking Vigabatrin (VGB). Additionally, to investigate the role of cumulative dosage, the role of VGB alone or in combination with other anticonvulsants, and whether recent discontinuance of VGB affects electroretinal function as measured by the electroretinogram (ERG). DESIGN: Retrospective, comparative case series. PARTICIPANTS: Forty patients (18 male, 22 female) with a mean age of 35 years were studied as three groups: the VGB multitherapy group (n = 24) included those taking VGB with other anticonvulsants, the VGB monotherapy group (n = 9) included those taking VGB alone, and the off-VGB group (n = 7) included those who had discontinued VGB in the last 6 months. METHODS: Scotopic flash, photopic flash, and 30-Hz flicker ERG results were recorded according to the International Society for Clinical Electrophysiology of Vision (ISCEV) standard. The clinical electro-oculogram (EOG) results were recorded according to the ISCEV standard. MAIN OUTCOME MEASURES: Implicit time and amplitudes of the A- and B-waves of the flash and 30-Hz flicker ERGs were recorded. Summed amplitude of the first three oscillatory potential wavelets were recorded. The light-peak to-dark-trough Arden ratio of the EOG was evaluated. RESULTS: Although photopic ERG B-wave reduction was most frequent in patients in the VGB multitherapy group (48% of eyes), a significant number of eyes in all three groups had scotopic ERG B-wave reduction. The 30-Hz flicker ERG result was abnormally reduced in all three groups. There was no significant difference in the frequency of occurrence in ERG result abnormalities between the VGB monotherapy and VGB multitherapy groups. The EOG results revealed reduced Arden ratios in all three groups; however, there was a significantly lower frequency of EOG abnormalities noted in the off-VGB group (P = 0. 0373). There was no statistically significant relationship between the frequency of electrodiagnostic abnormalities and the duration of use or the total cumulative dosage of Vigabatrin in any of the three groups. CONCLUSIONS: These findings of scotopic ERG result abnormalities suggest that VGB alone has an effect on inner electroretinal function at the level of the Müller cell. Concomitant EOG abnormalities suggest a substantial effect of VGB on outer retinal function that may be reversible after cessation of VGB treatment.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

S G Coupland, D H Zackon, B C Leonard, T M Ross. 2001. Vigabatrin effect on inner retinal function.. https://doi.org/10.1016/s0161-6420(01)00638-8

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Gamma-vinyl GABA, an irreversible inhibitor of GABA transaminase, alters the acquisition and expression of cocaine-induced sensitization in male rats.

We examined the effect of (+/-)-gamma-vinyl GABA (GVG, Vigabatrin), an irreversible inhibitor of the enzyme GABA transaminase, on the acquisition and expression of cocaine-induced sensitization in albino male Sprague-Dawley rats. Animals received a single injection of 1 ml/kg i.p. of 0.9% saline or 15 mg/kg i.p. of (-)-cocaine and locomotor activity was assessed using automated locomotor cages and stereotyped behaviors were scored using a 4-point rating scale (Day 1). Subsequently, animals were given 15 mg/kg i.p. of cocaine every 48 h in their home cage for 1 week (Days 3, 5, and 7) and then given no treatment for 1 week. A challenge injection of 15 mg/kg i.p. of cocaine, but not vehicle, produced a significant increase in locomotor activity and stereotyped behaviors on Day 15 compared to animals that received cocaine on Day 1. Administration of 75 mg/kg i.p. of GVG 2.5 h before the cocaine injections did not significantly alter the acquisition of cocaine-induced locomotor sensitization. However, 150 mg/kg i.p. of GVG significantly attenuated the acquisition of cocaine-induced locomotor sensitization. Administration of 150 mg/kg i.p. of GVG 2.5 h before the cocaine challenge injection on Day 15 significantly attenuated the expression of cocaine-induced locomotor sensitization. Acquisition and expression of cocaine-induced sensitization of stereotypy was also significantly attenuated by 150 mg/kg i.p. of GVG. Since sensitization may be one of the factors involved in relapse to drug use, the present results, in combination with previous findings that GVG blocks the rewarding and incentive motivating effects of cocaine, suggest that GVG might prove useful in the treatment of cocaine addiction.

4-Aminobutyrate Transaminase↗

Inactivation and inhibition of gamma-aminobutyric acid aminotransferase by conformationally restricted vigabatrin analogues.

Four cyclohexene analogues of gamma-aminobutyric acid (GABA) and beta-alanine were designed as conformationally rigid analogues of the epilepsy and drug addiction drug vigabatrin and as potential mechanism-based inactivators of gamma-aminobutyric acid aminotransferase (GABA-AT). The corresponding cyclopentene analogues were previously reported to be inhibitors, but not inactivators, of GABA-AT (Qiu, J.; Pingsterhaus, J.; Silverman, R. B. J. Med. Chem. 1999, 42, 4725-4728). cis-3-Aminocyclohex-4-ene-1-carboxylic acid (3) and cis-2-aminocyclohex-3-ene-1-carboxylic acid (5) showed time- and concentration-dependent, irreversible inactivation of GABA-AT. In both cases, the inactivations are protected by substrate, indicating that they are active site-directed. trans-3-Aminocyclohex-4-ene-1-carboxylic acid (4) and trans-2-aminocyclohex-3-ene-1-carboxylic acid (6) are not inactivators but are competitive reversible inhibitors of GABA-AT. Unlike the cyclopentene analogues, there appears to be sufficient ring flexibility to allow inactivation to occur. The orientation of the carboxylic and amino groups of these analogues is important for their binding to GABA-AT. Molecular modeling of GABA-AT with 3-6 and molecular dynamics simulations with vigabatrin bound provide rationalizations for the inhibitory properties of these compounds.

4-Aminobutyrate Transaminase↗

Detection of molecules related to the GABAergic system in a single-cell eukaryote, Paramecium primaurelia.

Gamma-aminobutyric acid (GABA)-related molecules were identified in Paramecium primaurelia by immunocytochemical methods, and GABA(A) receptors by their histochemical BODIPY-binding sites. Confocal microscope analysis showed different localizations according to the stages of the developmental cycle. A comparison was made with the cholinergic molecules, such as the acetylcholine biosynthetic enzyme (choline acetyltransferase), in double-labelled cells by confocal microscopy. In vivo experiments suggested the involvement of GABA-related molecules in cell-cell interaction.

4-Aminobutyrate Transaminase↗