Synergism of lacosamide with established antiepileptic drugs in the 6-Hz seizure model in mice

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dc.contributor.author Shandra, A. en
dc.contributor.author Shandra, P. en
dc.contributor.author Kaschenko, O. en
dc.contributor.author Matagne, A. en
dc.contributor.author Stohr, T. en
dc.date.accessioned 2020-07-28T06:41:02Z
dc.date.available 2020-07-28T06:41:02Z
dc.date.issued 2013
dc.identifier.citation Synergism of lacosamide with established antiepileptic drugs in the 6-Hz seizure model in mice / A. Shandra, P. Shandra, O. Kaschenko et al. // Epilepsia. 2013. N 54 (7). P. 1167–1175. en
dc.identifier.uri https://repo.odmu.edu.ua:443/xmlui/handle/123456789/7655
dc.description.abstract Lacosamide (LCM, Vimpat) is an anticonvulsant with a unique mode of action. This provides lacosamide with the potential to act additively or even synergistically with other antiepileptic drugs (AEDs). The objective of this study was to determine the presence of such interactions by isobolographic analysis. Methods: The anticonvulsant effect of LCM in combination with other AEDs including carbamazepine (CBZ), phenytoin (PHT), valproate (VPA), lamotrigine (LTG), topiramate (TPM), gabapentin (GBP), and levetiracetam (LEV) at fixed dose ratios of 1:3, 1:1, and 3:1, was evaluated in the 6-Hz–induced seizure model in mice. In addition, the impact of the combinations of LCM with the other AEDs on motor coordination was assessed in the rotarod test. Finally, AED concentrations were measured in blood and brain to evaluate potential pharmacokinetic drug interactions. Key Findings: All studied AEDs produced dose-dependent anticonvulsant effects against 6-Hz–induced seizures. Combinations of LCM with CBZ, LTG, TPM, GBP, or LEV were synergistic. All other LCM/AED combinations displayed additive effects with a tendency toward synergism. Furthermore, no enhanced adverse effects were observed in the rotarod test by combining LCM with other AEDs. No pharmacokinetic interactions were seen on brain AED concentrations. Coadministration of LCM and TPM led to an increase in plasma levels of LCM, whereas the plasma concentration of PHT was increased by coadministration of LCM. Significance: The synergistic anticonvulsant interaction of LCM with various AEDs, without exacerbation of adverse motor effects, highlights promising properties of LCM as add-on therapy for drug refractory epilepsy. en
dc.language.iso en en
dc.subject Pharmacodynamic drug interactions en
dc.subject Pharmacokinetic drug interactions en
dc.subject Motor impairment en
dc.title Synergism of lacosamide with established antiepileptic drugs in the 6-Hz seizure model in mice en
dc.type Article en


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