Abstract
This study evaluated the interactions between tiagabine (TGB) and three conventional antiepileptic drugs (AEDs): valproate (VPA), carbamazepine (CBZ), and phenobarbital (PB) in amygdala-kindled rats, a reliable model of complex partial seizures in humans. Isobolographic analysis of interactions revealed that TGB interacted additively with all tested conventional AEDs for the fixed-ratio combinations of 1:3, 1:1, and 3:1. Evaluation of pharmacokinetic interactions between AEDs revealed that the observed additivity was pharmacodynamic in nature. TGB did not affect the plasma and brain concentrations of VPA, CBZ and PB. Similarly, none of the studied conventional AEDs changed the plasma or brain levels of TGB. Also, TGB, VPA, CBZ, and PB administered alone (at their median effective doses) and in combinations at the fixed-ratio of 1:1 did not impair motor performance evaluated in the chimney test. In conclusion, additivity between TGB and conventional AEDs in amygdala-kindled rats and lack of bidirectional pharmacokinetic interactions suggest that TGB appears to be a valuable drug for an add-on therapy of refractory complex partial seizures in humans.
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Acknowledgments
This study was supported by the grant from European Social Found (Agreement No Z/2.06./11/2.6/09/04/U/06/04). Special thanks for HPLC measurements are directed to Dr. G. Raszewski (Institute of Agricultural Medicine, Lublin, Poland).
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Borowicz, K.K., Zadrozniak, M., Luszczki, J.J. et al. Interactions between tiagabine and conventional antiepileptic drugs in the rat model of complex partial seizures. J Neural Transm 115, 661–667 (2008). https://doi.org/10.1007/s00702-007-0006-3
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DOI: https://doi.org/10.1007/s00702-007-0006-3