RESEARCH PAPER
Interactions between pregabalin and phenobarbital in the mouse maximal electroshock-induced seizure model: an isobolographic analysis
1
Department of Pathophysiology, Medical University, Lublin, Poland; Department of Physiopathology, Institute of Agricultural Medicine, Lublin, Poland
Corresponding author
Jarogniew J. Łuszczki
Department of Pathophysiology, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
Department of Pathophysiology, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
J Pre Clin Clin Res. 2009;3(2):103-109
KEYWORDS
pregabalinphenobarbitalisobolographic analysismaximal electroshockpharmacodynamic/pharmacokinetic interaction
ABSTRACT
The aim of this study was to characterize the anticonvulsant effects of pregabalin (PGB – a third-generation antiepileptic drug) in combination with phenobarbital (PB – a classical antiepileptic drug) in the mouse maximal electroshock (MES)-induced seizure model by using the type I isobolographic analysis for non-parallel dose-response relationship curves (DRRCs). Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25mA, 500V, 50Hz, 0.2s stimulus duration) delivered via auricular electrodes. Potential adverse-effect profiles of interaction of PGB with PB at the fixed-ratio of 1:1 in the MES test with respect to motor performance, long-term memory and skeletal muscular strength were measured together with total brain PB concentrations. In the mouse MES model, PGB administered singly had a DRRC non-parallel to that for PB. With type I isobolographic analysis for non-parallel DRRCs, the combination of PGB with PB at the fixed-ratio of 1:1 exerted additive interaction. In combination, neither motor coordination, long-term memory nor muscular strength were affected. Pharmacokinetic estimation of total brain PB concentrations revealed that PGB did not affect total brain concentrations of PB in experimental animals. In conclusion, the additive interaction between PGB and PB is worthy of consideration while extrapolating the results from this study to clinical settings.
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