Interaction of oxcarbazepine with phenobarbital in the mouse pentylenetetrazole-induced seizure model: an isobolographic analysis

Combination therapy with two or three antiseizure medications (ASMs) is sometimes a preferred method of treatment in epilepsy patients. (1) Background: To detect the most beneficial combination among three ASMs, a screen test evaluating in vivo interactions with respect to their anticonvulsant properties, was conducted on albino Swiss mice; (2) Methods: Classification of interactions among lacosamide (LCM) and selected second-generation ASMs (lamotrigine (LTG), pregabalin (PGB), oxcarbazepine (OXC), and topiramate (TPM)) was based on the isobolographic analysis in the mouse maximal electroshock-induced seizure (MES) model. Interactions among LCM and second-generation ASMs were visualized using a polygonogram; (3) Results: In the mouse MES model, synergy was observed for the combinations of LCM + TPM + PGB and LCM + OXC + PGB. Additivity was reported for the other combinations tested i.e., LCM + LTG + TPM, LCM + LTG + PGB, LCM + LTG + OXC, and LCM + OXC + TPM in this seizure model. No adverse effects associated with triple ASM combinations, containing LCM and second-generation ASMs were observed in mice; (4) Conclusions: The combination of LCM + TPM + PGB was the most beneficial combination among the tested in this study, offering synergistic suppression of tonic-clonic seizures in mice subjected to the MES model. Both the isobolographic analysis and polygonogram method can be recommended for experimental epileptology when classifying interactions among the ASMs.

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INTERACTION OF THREE-DRUG COMBINATION OF LACOSAMIDE, CARBAMAZEPINE AND PHENOBARBITAL IN THE MOUSE MAXIMAL ELECTROSHOCK-INDUCED SEIZURE MODEL – AN ISOBOLOGRAPHIC ANALYSIS

Health Problems of Civilization ◽

10.5114/hpc.2016.58209 ◽

2016 ◽

Vol 1 ◽

pp. 55-61 ◽

Cited By ~ 11

Author(s):

Maria W. Kondrat-Wróbel ◽

Jarogniew J. Łuszczki

Keyword(s):

Drug Combination ◽

Maximal Electroshock ◽

Isobolographic Analysis ◽

Seizure Model

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Additive interaction of levetiracetam with lamotrigine in the mouse 6 Hz psychomotor seizure model – an isobolographic analysis

Current Issues in Pharmacy and Medical Sciences ◽

10.12923/j.2084-980x/26.1/a.18 ◽

2015 ◽

Vol 26 (1) ◽

pp. 82-87

Keyword(s):

Dose Response ◽

Seizure Activity ◽

Response Relationship ◽

Dose Response Relationship ◽

Additive Interaction ◽

Isobolographic Analysis ◽

Psychomotor Seizure ◽

Seizure Model ◽

A Current ◽

Anticonvulsant Effects

The aim of this study was to characterize the anticonvulsant effects of levetiracetam (LEV) in combination with lamotrigine (LTG – a second-generation antiepileptic drug), in the mouse 6 Hz psychomotor seizure model. Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes and isobolographic analysis for parallel dose-response relationship curves (DRRCs) was used to characterize the consequent anticonvulsant interactions between the drug combinations. Results indicated that LEV administered singly was associated with a DRRC that was parallel to that for LTG. With isobolography for parallel DRRCs, the combination of LEV with LTG at three fixed-ratios of 1:3, 1:1 and 3:1 exerted additive interaction. LEV combined with LTG exerted additive interaction in the mouse 6 Hz psychomotor seizure model.

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