Effect of gabapentin on the anticonvulsant activity of antiepileptic drugs against electroconvulsions in mice: an isobolographic analysis.
OBJECTIVE
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 (< or =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.
Department of Pathophysiology and Department of Pharmacology and Toxicology, Medical University, and Isotope Laboratory, Institute of Agricultural Medicine, Lublin, Jaczewskiego, Poland.
Kinga K
KK
Borowicz
Mariusz
M
Swiader
Jarogniew
J
Luszczki
Stanislaw J
SJ
Czuczwar
D000085:Acetates / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004597:Electroshock; D004827:Epilepsy / Q000188:drug therapy; D000077206:Gabapentin; D006801:Humans; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011897:Random Allocation; D012640:Seizures / Q000097:blood / Q000517:prevention & control*; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin