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Effect of Gabapentin on the Anticonvulsant Activity of Antiepileptic Drugs against Electroconvulsions in Mice: An Isobolographic Analysis
Author(s) -
Borowicz Kinga K.,
Swiader Mariusz,
Luszczki Jarogniew,
Czuczwar Stanislaw J.
Publication year - 2002
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.2002.34301.x
Subject(s) - gabapentin , carbamazepine , lamotrigine , anticonvulsant , phenobarbital , phenytoin , pharmacology , medicine , epilepsy , valproic acid , adverse effect , pharmacokinetics , drug interaction , anesthesia , alternative medicine , pathology , psychiatry
Summary: Purpose: The objective of this study was the isobolographic evaluation of the interactions between the novel antiepileptic drug (AED) gabapentin (GBP) and a number of other AEDs against electroconvulsion‐induced convulsions in mice. Methods: Electroconvulsions were produced by means of an alternating current (ear‐clip electrodes, 0.2‐s stimulus duration, tonic hindlimb extension taken as the end point). Adverse effects were evaluated with the chimney test (motor performance) and passive‐avoidance task (long‐term memory). Plasma levels of AEDs were measured by immunofluorescence or high‐pressure liquid chromatography. Results: GBP (≤50 mg/kg) remained ineffective on the electroconvulsive threshold. According to the isobolographic analysis, GBP appears to act synergistically with carbamazepine, valproate, phenytoin, phenobarbital (PB), lamotrigine (LTG), and LY 300164. The pharmacokinetic events may be responsible for the interactions of GBP/PB and GBP/LTG, because only PB and LTG significantly elevated the plasma concentration of this AED. Conversely, GBP did not affect the plasma levels of other AEDs used in this study. No adverse effects were induced by combinations of GBP with these AEDs. Conclusions: The isobolographic analysis revealed that combinations of GBP with other AEDs generally results in synergistic (supraadditive) interactions.