Effect of ethacrynic acid on the anticonvulsant activity of the second-generation antiepileptics against maximal electroshock-induced seizures in mice.
Recent experimental studies show that ethacrynic acid (ETA), a loop diuretic, exerts the anticonvulsant activity. Therefore, we tested the effect of ETA on the protective action of some second-generation antiepileptic drugs (oxcarbazepine [OXC], lamotrigine [LTG] and topiramate [TPM]) in the mouse maximal electroshock seizure (MES) model. ETA was administered acutely (50 and 100 mg/kg i.p.) or chronically, for 7 days (12.5 mg/kg i.p.). Both ETA acute (up to 100 mg/kg) and chronic (up to 12.5 mg/kg) treatment did not influence the threshold for electroconvulsions. In the MES test, ETA (100 mg/kg) potentiated the protective activity of TPM, decreasing its ED(50) value from 38.1 to 18.7 mg/kg (P<0.01). In contrast, ETA (100 mg/kg) remained without effect on the anticonvulsant action of the other antiepileptics (OXC and LTG) in mice. Chronic administration of ETA (12.5 mg/kg) did not affect the protective action of tested antiepileptics. The observed interaction between acute ETA and TPM was pharmacodynamic in nature because neither plasma nor total brain TPM concentrations were altered after injection of ETA.These results indicate existing interactions between ETA and TPM, which may have some clinical importance for epileptic patients treated with TPM and additionally ETA due to other medical causes.
Department of Physiopathology, Institute of Agricultural Medicine, Lublin, Poland. lukaw@mp.pl
Krzysztof
K
Łukawski
Grazyna
G
Swiderska
Stanisław J
SJ
Czuczwar
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D001923:Brain Chemistry; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004597:Electroshock; D004976:Ethacrynic Acid / Q000008:administration & dosage*; D005632:Fructose / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology; D000077213:Lamotrigine; D008297:Male; D051379:Mice; D009048:Motor Skills / Q000187:drug effects; D000078330:Oxcarbazepine; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology*; D018709:Statistics, Nonparametric; D000077236:Topiramate; D014227:Triazines / Q000494:pharmacology
D000927:Anticonvulsants; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D002220:Carbamazepine; D004976:Ethacrynic Acid; D000077213:Lamotrigine; D000078330:Oxcarbazepine