Levetiracetam selectively potentiates the acute neurotoxic effects of topiramate and carbamazepine in the rotarod test in mice

Łuszczki, Jarogniew J.; Andres, Marta M; Czuczwar, Piotr; Cioczek-Czuczwar, Anna; Wojcik-Cwikla, Joanna; Ratnaraj, Neville; Patsalos, Philip N.; Czuczwar, Stanisław J.

doi:10.1016/j.euroneuro.2005.03.005

Cited by 40 publications

(34 citation statements)

References 35 publications

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“…However, it should be highlighted that the evaluation of acute neurotoxic effects in this study was performed only at doses of LEV and the various AEDs that corresponded to the ED 50 mix at the maximal fixed‐ratio combination tested. Moreover, it is notable that the median toxic dose (TD 50 ) of LEV with respect to the impairment of motor coordination of animals in the rotarod test, denoted in our previous study, was 1,601 (1,324–1,935) mg/kg (67). Furthermore, we have reported that LEV (administered at a constant dose of 150 mg/kg) potentiated the acute neurotoxic effects of TPM and CBZ in the rotarod test in mice, reducing considerably their TD 50 values from 423 to 246 mg/kg and from 53.6 to 37.3 mg/kg, respectively (67).…”

Section: Discussionmentioning

confidence: 83%

“…The remaining fixed ratios tested for these AED combinations were indifferent (Tables 2 and 3). The observed synergistic interactions between LEV and CBZ and OXC may probably be attributable to the fact that LEV (at doses >100 mg/kg) can significantly increase the threshold for electroconvulsions in mice (67). Conversely, additional mechanisms could include an effect of LEV on N‐ and P/Q‐types HVA Ca 2+ channels and an effect of CBZ and OXC on Na + ‐channel blockade or activation of the adenosinergic inhibitory neurotransmitter system (68).…”

Section: Discussionmentioning

confidence: 99%

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Pharmacodynamic and Pharmacokinetic Characterization of Interactions between Levetiracetam and Numerous Antiepileptic Drugs in the Mouse Maximal Electroshock Seizure Model: An Isobolographic Analysis

et al. 2006

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Summary:Purpose: Approximately 30% of patients with epilepsy do not experience satisfactory seizure control with antiepileptic drug (AED) monotherapy and often require polytherapy. The potential usefulness of AED combinations, in terms of efficacy and adverse effects, is therefore of major importance. The present study sought to identify potentially useful AED combinations with levetiracetam (LEV)Methods: With isobolographic analysis, the mouse maximal electroshock (MES)-induced seizure model was investigated with regard to the anticonvulsant effects of carbamazepine (CBZ), phenytoin, phenobarbital (PB), valproate, lamotrigine, topiramate (TPM), and oxcarbazepine (OXC), administered singly and in combination with LEV. Acute adverse effects were ascertained by use of the chimney test evaluating motor performance and the step-through passive-avoidance task assessing long-term memory. Brain AED concentrations were determined to ascertain any pharmacokinetic contribution to the observed antiseizure effect.Results: LEV in combination with TPM, at the fixed ratios of 1:2, 1:1, 2:1, and 4:1, was supraadditive (synergistic) in the MES test. Likewise, the combination of LEV with CBZ (at the fixed ratio of 16:1) and LEV with OXC (8:1 and 16:1) were supraadditive. In contrast, all other LEV/AED combinations displayed additivity. Furthermore, none of the investigated LEV/AED combinations altered motor performance and long-term memory. LEV brain concentrations were unaffected by concomitant AED administration, and LEV had no significant effect on brain concentrations of concomitant AEDs.Conclusions: These preclinical data would suggest that LEV in combination with TPM is associated with beneficial anticonvulsant pharmacodynamic interactions. Similar, but less profound effects were seen with OXC and CBZ.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Pharmacodynamic and Pharmacokinetic Characterization of Interactions between Levetiracetam and Numerous Antiepileptic Drugs in the Mouse Maximal Electroshock Seizure Model: An Isobolographic Analysis

et al. 2006

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“…It has minimal plasma protein binding, therefore; there is no significant interaction with other drugs for binding sites. The drug is excreted renally, and there is no hepatic metabolism (5,6). In a previous study, side effects profile of levetiracetam in children younger than four years were reported as irritability, somnolence, difficulty in sleeping, dizziness, rash, decreased appetite and hypertrichosis (2).…”

Section: Discussionmentioning

confidence: 99%

Two Cases of Levetiracetam Overdose Without Any Serious Side Effects

2017

GMJ

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“…On the first day, before treating the mice with any drugs the animals were pre-trained and only the mice were able to remain on the rotating rod (6 rpm) for 60s were chosen for the experiment. On the test day, the mice were placed on rod and the latency to fall during 120s was recorded (Luszczki et al, 2005).…”

Section: Rotarodmentioning

confidence: 99%