title: Effect of combined treatment with diuretics and gabapentin on convulsive threshold in mice.
abstract: Research data show that diuretics can have anticonvulsant properties. This study examined effects of ethacrynic acid, a loop diuretic, and hydrochlorothiazide, a thiazide-type diuretic, on the anticonvulsant activity of gabapentin, a newer antiepileptic drug, in the maximal electroshock seizure threshold test in mice. Diuretics were administered intraperitoneally (ip.) both acutely (single dose) and chronically (once daily for seven days). Electroconvulsions were produced by an alternating current (50 Hz, 500 V, 0.2 s stimulus duration) delivered via ear-clip electrodes by a generator. Additionally, the influence of combined treatment with the diuretics and gabapentin on motor performance in the chimney test has been assessed. In the current study, ethacrynic acid at the chronic dose of 12.5 mg/kg and the single dose of 100 mg/kg did not affect the anticonvulsant activity of gabapentin. Similarly, hydrochlorothiazide (100 mg/kg), both in acute and chronic experiments, had no effect on the gabapentin action. On the other hand, in the chimney test, the combined treatment with ethacrynic acid (100 mg/kg) and gabapentin (50 mg/kg) significantly impaired motor performance in mice. Based on the current preclinical findings, it can be suggested that the diuretics should not affect the anticonvulsant action of gabapentin in epileptic patients. However, the combination of ethacrynic acid with gabapentin may cause neurotoxicity.
authors.affiliation: Department of Physiopathology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-090 Lublin, Poland. lukaw@mp.pl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Łukawski
authors.forename: Grajyna
authors.initials: G
authors.lastname: Swiderska
authors.forename: Stanisław J
authors.initials: SJ
authors.lastname: Czuczwar
mesh_terms: D000588:Amines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004347:Drug Interactions; D004597:Electroshock; D004976:Ethacrynic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000077206:Gabapentin; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000503:physiopathology / Q000523:psychology; D012640:Seizures / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D004232:Diuretics; D006852:Hydrochlorothiazide; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D004976:Ethacrynic Acid