title: Influence of ethacrynic acid on the anticonvulsant activity of conventional antiepileptic drugs in the mouse maximal electroshock seizure model.
abstract: The aim of this study was to determine whether ethacrynic acid (EA), a loop diuretic with anticonvulsant activity, would affect the protective action of the conventional antiepileptics (AEDs) carbamazepine (CBZ), phenytoin (PHT), valproate (VPA) and phenobarbital (PB) in the mouse maximal electroshock seizure (MES) model. The effects of acute and chronic treatment with EA on these AEDs were examined. At a single dose of 100 mg/kg ip, EA enhanced the antielectroshock activity of VPA, decreasing its ED₅₀ value from 225.6 to 146.6 mg/kg (p < 0.05), but enhancement was not observed following continuous administration of EA (12.5 mg/kg) for seven days. Combined treatment of EA with other AEDs had no effect on their ED₅₀ values. The observed interaction between EA and VPA was pharmacodynamic in nature as EA did not alter free plasma (non-protein-bound) and total brain concentrations of VPA. Taking into consideration the clinical use of both drugs, this interaction between EA and VPA can be important for patients receiving these drugs.
authors.affiliation: Department of Physiopathology, Institute of Agricultural Medicine, Jaczewskiego 2, PL20-090 Lublin, Poland. lukaw@mp.pl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Łukawski
authors.forename: Grażyna
authors.initials: G
authors.lastname: Swiderska
authors.forename: Jarogniew J
authors.initials: JJ
authors.lastname: Łuszczki
authors.forename: Stanisław J
authors.initials: SJ
authors.lastname: Czuczwar
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002220:Carbamazepine / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D004232:Diuretics / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004597:Electroshock; D004976:Ethacrynic Acid / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D010634:Phenobarbital / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D010672:Phenytoin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology; D014635:Valproic Acid / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D004232:Diuretics; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D004976:Ethacrynic Acid; D010634:Phenobarbital