Do Antiepileptic Drugs Exacerbate Seizures?

Loiseau, P

doi:10.1111/j.1528-1157.1998.tb01267.x

Cited by 24 publications

(11 citation statements)

References 30 publications

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“…A growing body of evidence has suggested that clinical use of conventional and novel AEDs may sometimes contribute to the aggravation of seizures (Perucca et al, 1998;Murphy and Delanty, 2000). Among the AEDs, possessing a high propensity for inducing the seizures, there are: VGB, TGB, or GBPFwhich selectively affect the GABA-ergic system (Loiseau, 1998). Also, it was observed that patients on addon therapy, taking VGB or GBP, two to four times frequently experienced convulsions than patients medicated only with CBZ or VPA (Elger et al, 1998).…”

Section: Controlmentioning

confidence: 99%

Tiagabine Synergistically Interacts with Gabapentin in the Electroconvulsive Threshold Test in Mice

Łuszczki

Świąder

Parada-Turska

et al. 2003

Neuropsychopharmacol

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Polytherapy, based on the rational combining of antiepileptic drugs (AEDs), is required for patients with drug-resistant epilepsy. In such cases, the combinations of AEDs usually offer a significant enhancement of their protective effects against seizures. There has appeared a hypothesis that combining two AEDs, influencing the same neurotransmitter system, results in the potentialization of their anticonvulsant effects. For corroborating this hypothesis, a pharmacological character of interaction between tiagabine (TGB) and gabapentin (GBP)Ftwo novel AEDs affecting the GABA-ergic system, in the maximal electroshock seizure threshold (MEST)-test in mice was evaluated. TGB at the dose of 4 mg/kg and GBP at 75 mg/kg significantly raised the electroconvulsive threshold. Further, using the isobolographic calculations, TGB was coadministered with GBP at three fixed-ratios (1 : 3, 1 : 1, and 3 : 1) of their respective protective drug doses. All examined combinations of TGB with GBP exerted supra-additive (synergistic) interactions against MEST-induced seizures in mice. The interaction index, describing the strength and magnitude of interaction, ranged between 0.25 and 0.50 indicating supraadditivity. Adverse (neurotoxic) effects were evaluated in the chimney (motor performance) and the step-through, light-dark passive avoidance (long-term memory) tests in mice. The examined combinations of TGB with GBP did not affect the motor coordination, except for the fixed-ratio of 1 : 1, at which significant impairment of motor performance was observed. Moreover, all combinations selectively impaired the acquisition of the task in the passive avoidance test, having no impact on consolidation and retrieval in the longterm memory test. The pain threshold test revealed that the observed disturbances in the passive avoidance testing resulted presumably from the antinociceptive activity of these AEDs in combinations. After lengthening the exposing time to the direct current stimulus in the passive avoidance test from 2 to 6 s, the acquisition of the task, in animals receiving the combinations of TGB and GBP was not impaired. Neither the plasma, nor brain concentrations of GBP were affected by TGB application, so pharmacokinetic events that might negatively influence the observed effects are not probable. Results of this study clearly indicate that the activation of the same neurotransmitter system (GABA-ergic) leads to a synergistic interaction. The pain threshold test is a very good paradigm for screening the antinociceptive properties of AEDs, which may disturb the long-term memory testing in animals. Combinations of TGB with GBP (very promising from a preclinical point of view) should be clinically verified for elaborating the most effective treatment regimen in patients with intractable seizures.

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Section: Controlmentioning

confidence: 99%

Tiagabine Synergistically Interacts with Gabapentin in the Electroconvulsive Threshold Test in Mice

Łuszczki

Świąder

Parada-Turska

et al. 2003

Neuropsychopharmacol

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“…Although this paradoxical phenomenon has been recognized for decades, only few systematic studies have addressed this issue [18]. Perruca and co-workers provided a critical review of all available reports on this topic and suggested that there are two distinct situations during which seizure aggravation may occur [19].…”

Section: Discussionmentioning

confidence: 97%

Non convulsive status epilepticus after replacement of valproate with lamotrigine

Trinka¹,

Dilitz²,

Unterberger³

et al. 2002

Journal of Neurology

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“…There is growing awareness that antiepileptic drugs can sometimes worsen epileptic disorders (Perucca et al 1998) by disrupting the equilibrium between excitatory and inhibitory circuits (Loiseau 1998). In the present study, we found that mice pretreated subchronically with antiepileptic drugs enhancing GABAergic neurotransmission showed an augmented susceptibility to PTZ-induced seizures, reduced BDZ receptor binding, or both.…”

Section: Discussionmentioning

confidence: 99%

Subchronic treatment with antiepileptic drugs modifies pentylenetetrazol-induced seizures in mice: Its correlation with benzodiazepine receptor binding

Rocha¹

2008

NDT

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Experiments using male CD1 mice were carried out to investigate the effects of subchronic (daily administration for 8 days) pretreatments with drugs enhancing GABAergic transmission (diazepam, 10 mg/kg, ip; gabapentin, 100 mg/kg, po; or vigabatrin, 500 mg/kg, po) on pentylenetetrazol (PTZ)-induced seizures, 24 h after the last injection. Subchronic administration of diazepam reduced latencies to clonus, tonic extension and death induced by PTZ. Subchronic vigabatrin produced enhanced latency to the fi rst clonus but faster occurrence of tonic extension and death induced by PTZ. Subchronic gabapentin did not modify PTZ-induced seizures. Autoradiography experiments revealed reduced benzodiazepine receptor binding in several brain areas after subchronic treatment with diazepam or gabapentin, whereas subchronic vigabatrin did not induce signifi cant receptor changes. The present results indicate differential effects induced by the subchronic administration of diazepam, vigabatrin, and gabapentin on the susceptibility to PTZ-induced seizures, benzodiazepine receptor binding, or both.

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Do Antiepileptic Drugs Exacerbate Seizures?

Cited by 24 publications

References 30 publications

Tiagabine Synergistically Interacts with Gabapentin in the Electroconvulsive Threshold Test in Mice

Tiagabine Synergistically Interacts with Gabapentin in the Electroconvulsive Threshold Test in Mice

Non convulsive status epilepticus after replacement of valproate with lamotrigine

Subchronic treatment with antiepileptic drugs modifies pentylenetetrazol-induced seizures in mice: Its correlation with benzodiazepine receptor binding

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