Interactions of pregabalin with gabapentin- levetiracetam- tiagabine and vigabatrin in the mouse maximal electroshock-induced seizure model- a type II isobolographic analysis-

Authors
J. Luszczki, D. Filip, M. Florek-Luszczki.

Lab
Medical University of Lublin, Department of Pathophysiology, Lublin, Poland.

Journal
Epilepsy research

Abstract
The aim of this study was to characterize the anticonvulsant effects of pregabalin in combination with four second-generation antiepileptic drugs (i.e., gabapentin, levetiracetam, tiagabine, and vigabatrin) in the mouse maximal electroshock (MES)-induced seizure model by using the type II isobolographic analysis. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. The combination of pregabalin with gabapentin at the fixed-ratio of 1:1 was supra-additive (synergistic) in terms of seizure suppression while the combinations at the fixed-ratios of 2:1 and 4:1 were additive in the mouse MES model. Similarly, the combination of pregabalin with tiagabine at the fixed-ratio of 25:1 was supra-additive, whereas the combinations at the fixed-ratios of 100:1 and 50:1 were additive in the mouse MES model. Pregabalin with levetiracetam and vigabatrin at the fixed-ratios of 1:1, 2:1 and 4:1 were additive in this seizure model. The combinations of pregabalin with gabapentin (1:1) and pregabalin with tiagabine (25:1) appear to be favorable combinations exerting supra-additive interaction in suppressing MES-induced seizures. Pregabalin in combination with levetiracetam and vigabatrin appears to be neutral producing only additivity in the mouse MES model.

BIOSEB Instruments Used:
Grip strength test (BIO-GS3)