Abstract:
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 (< 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.
journal_name
Epilepsiajournal_title
Epilepsiaauthors
Borowicz KK,Swiader M,Luszczki J,Czuczwar SJdoi
10.1046/j.1528-1157.2002.34301.xsubject
Has Abstractpub_date
2002-09-01 00:00:00pages
956-63issue
9eissn
0013-9580issn
1528-1167pii
epi34301journal_volume
43pub_type
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