ArticlePharmacological reports : PR2020
Sub-additive (antagonistic) interaction of lacosamide with lamotrigine and valproate in the maximal electroshock-induced seizure model in mice: an isobolographic analysis.
Article in Pharmacological reports : PR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed, 5 citations in OpenAlex.
- Interactions among Lacosamide and Second-Generation Antiepileptic Drugs in the Tonic-Clonic Seizure Model in Mice.International journal of molecular sciences · 2021Article
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7 authors at 4 institutions in 1 country.
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Abstract
backgroundLaunching polytherapy with two or three antiseizure drugs (ASDs) in patients with epilepsy is still problematic. The choice of ASDs to combine them together is usually based on clinicians' experience and it requires knowledge about mechanisms of action of the studied ASDs and their drug-drug interactions, whose nature may be favorable, neutral or unfavorable. To characterize three-drug interaction among lacosamide (LCM), lamotrigine (LTG) and valproate (VPA), the type I isobolographic analysis was used. The antiseizure effects of three-drug combination were analyzed in a model of maximal electroshock-induced seizures (MES) in albino Swiss mice. MATERIALS AND
methodsThe seizure activity in mice was evoked by alternating current stimulation (25 mA, 500 V, 50 Hz, 0.2 s). Both, the type I isobolographic analysis and the test of parallelism of dose-response effects of the ASDs were used so as to properly classify interaction among three ASDs, administered in a fixed ratio combination of 1:1:1.
resultsThe three-drug mixture of LCM, LTG and VPA at the fixed ratio of 1:1:1 protected the experimental mice from MES-induced seizures; however, the reported interaction was sub-additive (antagonistic; p < 0.01) with isobolography.
conclusionThe antagonistic pharmacodynamic interaction among LCM, LTG and VPA in the MES test in mice cannot be transferred to clinical settings and this unfavorable combination should not be recommended for patients with epilepsy.
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