title: Interactions of pregabalin with gabapentin, levetiracetam, tiagabine and vigabatrin in the mouse maximal electroshock-induced seizure model: a type II isobolographic analysis.
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.
authors.affiliation: Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, PL 20-090 Lublin, Poland. jarogniew.luszczki@gmail.com
authors.forename: Jarogniew J
authors.initials: JJ
authors.lastname: Luszczki
authors.forename: Damian
authors.initials: D
authors.lastname: Filip
authors.forename: Magdalena
authors.initials: M
authors.lastname: Florek-Luszczki
mesh_terms: D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects; D016001:Confidence Intervals; D003509:Cyclohexanecarboxylic Acids; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004597:Electroshock / Q000009:adverse effects*; D000077206:Gabapentin; D018737:Hand Strength / Q000502:physiology; D000077287:Levetiracetam; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010889:Piracetam / Q000031:analogs & derivatives; D000069583:Pregabalin; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D000077287:Levetiracetam; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D020888:Vigabatrin; D010889:Piracetam