Determination of GABA and vigabatrin in human plasma by a rapid and simple HPLC method: correlation between clinical response to vigabatrin and increase in plasma GABA

Löscher, Wolfgang; Fassbender, C. P.; Gram, Lennart; Gramer, Martina; Hörstermann, Dirk; Zahner, B.; Stefan, Hermann

doi:10.1016/0920-1211(93)90049-d

Cited by 55 publications

(15 citation statements)

References 29 publications

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“…This activity is resistant to classic AEDs. Among newer AEDs, a similar effect was seen only with 5 mM VGB after 60-min application (data not published), a concentration much is clearly above plasma levels observed during treatment (26)(27)(28). The LRDs are also sen-sitive to NMDA-receptor antagonists such as ketamine, 2-amino-phosphonovaleric acid (APV), and dextrometorphan but not to antagonists that act on AMPAIkainate type of glutamate receptors (15,18,29,30).…”

Section: Discussionmentioning

confidence: 80%

Effects of Retigabine (D‐23129) on Different Patterns of Epileptiform Activity Induced by Low Magnesium in Rat Entorhinal Cortex Hippocampal Slices

Armand

Rundfeldt²,

Heinemann

2000

Epilepsia

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Summary:Purpose: The objective of this study was to evaluate the effect of a new antiseizure drug, retigabine (D-23129; N-(2-amino-4-[fluorobenzylamino]-phenyl) carbamic acid ethyl ester) on low-Mg*+-induced epileptiform discharges in rat in vitro.Methods: Three types of epileptiform discharges (recurrent short discharges in the hippocampus, seizure-like events, and late recurrent discharges in the entorhinal cortex) were elicited in rat combined entorhinal cortex-hippocampal slices by perfusion with low-Mg*+-artificial cerebrospinal fluid (ACSF). The antiepileptic properties of retigabine were evaluated as effect on the frequency and amplitude of the epileptiform activities as well as time of onset of the effect in the entorhinal cortex (EC) and in hippocampal area CAI (CAI) by using extracellular recording techniques.Results: Retigabine (20 pMj reversibly suppressed the recurrent short discharges otherwise sensitive only to high doses of valproate (VPA) but insensitive to standard antiepileptic drugs (AEDs) in CAI, whereas 10 pM reduced the frequency of discharges by 34 * 18.8%, with no significant effect on the amplitude. In EC, retigabine (50 p M ) reversibly suppressed the seizure-like events, whereas 20 blocked seizure-like events in 71.5% of the slices. The seizure-like events were also sensitive to standard AEDs. Late recurrent discharges in EC that are not blocked by standard AEDs were reversibly suppressed by retigabine (100 pMj, whereas 50 p M reduced the frequency of the discharges by 94.4 c 7.7%, and 20 pM, by 74.2 18.0%, with no significant effect on the amplitude.Conclusions: Retigabine is an effective AED with suppressive effects on recurrent short discharges and on late recurrent discharges normally insensitive to standard AEDs. Key Words: Retigabine-Epileptiform activities-Entorhinal cortex-Hippocampus-Low magnesium.Retigabine (D-23 129), a new antiseizure drug synthesized by ASTA Medica AG (Frankfurt, Germany), is a desazo analogue derivative of flupirtine. Retigabine has been shown to be an effective compound in a large variety of seizure models in vivo and in vitro (1). Retigabine is effective against maximal electroshock and subcutaneous pentylenetetrazol seizures (2,3), in the amygdala kindling model in rats (4), and in two genetic models of epilepsy, the audiogenic seizure DBA/2J mice and the genetically epilepsy-prone rats (5,6). In vitro, reti-

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Section: Discussionmentioning

confidence: 80%

Effects of Retigabine (D‐23129) on Different Patterns of Epileptiform Activity Induced by Low Magnesium in Rat Entorhinal Cortex Hippocampal Slices

Armand

Rundfeldt²,

Heinemann

2000

Epilepsia

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“…11). For instance, VGB acts by irreversible inhibition of the GABA‐degrading enzyme GABA aminotransferase (GABA‐T), thereby markedly increasing GABA levels in the brain, cerebrospinal fluid (CSF), and plasma of different species, including humans (151a–154). During prolonged treatment of mice with VGB via the drinking water, tolerance to the anticonvulsant effect was observed in the MES threshold test (155).…”

Section: Mechanisms Of Tolerance To Aedsmentioning

confidence: 99%

Experimental and Clinical Evidence for Loss of Effect (Tolerance) during Prolonged Treatment with Antiepileptic Drugs

Löscher

Schmidt²

2006

Epilepsia

217

141

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Summary: Development of tolerance (i.e., the reduction in response to a drug after repeated administration) is an adaptive response of the body to prolonged exposure to the drug, and tolerance to antiepileptic drugs (AEDs) is no exception. Tolerance develops to some drug effects much more rapidly than to others. The extent of tolerance depends on the drug and individual (genetic?) factors. Tolerance may lead to attenuation of side effects but also to loss of efficacy of AEDs and is reversible after discontinuation of drug treatment. Different experimental approaches are used to study tolerance in laboratory animals. Development of tolerance depends on the experimental model, drug, drug dosage, and duration of treatment, so that a battery of experimental protocols is needed to evaluate fully whether tolerance to effect occurs. Two major types of tolerance are known. Pharmacokinetic (metabolic) tolerance, due to induction of AED-metabolizing enzymes has been shown for most firstgeneration AEDs, and is easy to overcome by increasing dosage. Pharmacodynamic (functional) tolerance is due to "adaptation" of AED targets (e.g., by loss of receptor sensitivity) and has been shown experimentally for all AEDs that lose activity during prolonged treatment. Functional tolerance may lead to complete loss of AED activity and cross-tolerance to other AEDs. Convincing experimental evidence indicates that almost all first-, second-, and third-generation AEDs lose their antiepileptic activity during prolonged treatment, although to a different extent. Because of diverse confounding factors, detecting tolerance in patients with epilepsy is more difficult but can be done with careful assessment of decline during long-term individual patient response. After excluding confounding factors, tolerance to antiepileptic effect for most modern and old AEDs can be shown in small subgroups of responders by assessing individual or group response. Development of tolerance to the antiepileptic activity of an AED may be an important reason for failure of drug treatment. Knowledge of tolerance to AED effects as a mechanism of drug resistance in previous responders is important for patients, physicians, and scientists.

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“…For the analysis of VGB enantiomers in human serum or plasma we reported a method [6], but since the suggested linear relationship between both enantiomers [6,7] determination of the racemate concentration in serum or plasma will be suitable for routine therapeutic drug monitoring. This can be performed by high-performance liquid chromatography (HPLC) and fluorescence detection after rapid and simple precolumn derivatization using ophtaldialdehyde (OPA) and 2-mercaptoethanol [8,9]. Besides methods for the analysis of GBP alone [10][11][12] some papers describe the simultaneous determination of GBP and VGB [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous high-performance liquid chromatographic analysis of pregabalin, gabapentin and vigabatrin in human serum by precolumn derivatization with o-phtaldialdehyde and fluorescence detection

Vermeij

Edelbroek

2004

Journal of Chromatography B

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Determination of GABA and vigabatrin in human plasma by a rapid and simple HPLC method: correlation between clinical response to vigabatrin and increase in plasma GABA

Cited by 55 publications

References 29 publications

Effects of Retigabine (D‐23129) on Different Patterns of Epileptiform Activity Induced by Low Magnesium in Rat Entorhinal Cortex Hippocampal Slices

Effects of Retigabine (D‐23129) on Different Patterns of Epileptiform Activity Induced by Low Magnesium in Rat Entorhinal Cortex Hippocampal Slices

Experimental and Clinical Evidence for Loss of Effect (Tolerance) during Prolonged Treatment with Antiepileptic Drugs

Simultaneous high-performance liquid chromatographic analysis of pregabalin, gabapentin and vigabatrin in human serum by precolumn derivatization with o-phtaldialdehyde and fluorescence detection

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