Interaction between diuretics and tiagabine in the maximal electroshock seizure threshold test in mice
More details
Hide details
Department of Physiopathology, Institute of Agricultural Medicine, Lublin, Poland
Poland; Department of Pathophysiology, Medical University, Lublin, Poland
Corresponding author
Krzysztof Łukawski   

Department of Physiopathology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-090 Lublin, Poland.
J Pre Clin Clin Res. 2010;4(1):40-42
It has been reported that loop diuretics can aff ect the antiseizure action of valproate (VPA) and topiramate (TPM) in mice. This study evaluated the effect of ethacrynic acid (EA), a loop diuretic, and hydrochlorothiazide (HCTZ), a thiazide-type diuretic, on the anticonvulsant activity of tiagabine (TGB), a newer antiepileptic drug, in the maximal electroshock seizure threshold test. The threshold for electroconvulsions is regarded as an experimental model of tonic-clonic seizures in humans. Diuretics were administered intraperitoneally (i.p.) at single doses (acute treatment) or once daily for seven days (chronic administration). EA at subthreshold doses of 12.5 mg/kg (chronic) and 100 mg/kg (acute) did not affect the anticonvulsant activity of TGB. Similarly, HCTZ at the subthreshold dose of 100 mg/kg, both in acute and chronic experiments, remained without effect on the anticonvulsant action of TGB. From the preclinical point of view, the use of tested diuretics in epileptic patients receiving TGB is presumed neutral upon its anticonvulsant potency.
Brater DC: Diuretics. In: Munson PL, Mueller RA, Breese GR (Eds.): Principles of pharmacology. Basic concepts and clinical application. Chapman and Hall, New York, 1995, 657-672.
Seely JF, Dirks JH: Site of action of diuretic drugs. Kidney Int 1977, 11, 1-8.
Brater DC: Pharmacology of diuretics. Am J Med Sci 2000, 31, 38-50.
Haglund MM, Hochman DW: Furosemide and mannitol suppression of epileptic activity in the human brain. J Neurophysiol 2005, 94, 907- 918.
Hesdorff er DC, Stables JP, Hauser WA, Annegers JF, Cascino G: Are certain diuretics also anticonvulsants? Ann Neurol 2001, 50, 458- 462.
Reid KH, Guo SZ, Iyer VG: Agents which block potassium-chloride cotransport prevent sound-triggered seizures in post-ischemic audiogenic seizure-prone rats. Brain Res 2000, 864, 134-137.
Łukawski K, Świderska G, Czuczwar SJ: Eff ect of ethacrynic acid on the anticonvulsant activity of the second-generation antiepileptics against maximal electroshock-induced seizures in mice. Epilepsy Res 2009, 87, 190-196.
Łuszczki JJ, Sawicka KM, Kozinska J, Borowicz KK, Czuczwar SJ: Furosemide potentiates the anticonvulsant action of valproate in the mouse maximal electroshock seizure model. Epilepsy Res 2007, 76, 66-72.
Payne JA: Functional characterization of the neuronal-specifi c K-Cl cotransporter: implications for [K+]o regulation. Am J Physiol 1997, 273, C1516-C1525.
Payne JA, Stevenson TJ, Donaldson LF: Molecular characterization of a putative K-Cl co-transporter in rat brain: a neuronal-specifi c isoform. J Biol Chem 1996, 271, 16245-16252.
Gillen CM, Brill S, Payne JA, Forbush B 3rd: Molecular cloning and functional expression of the K-Cl cotransport from rabbit, rat, and human: a new member of the cation-chloride cotransporter family. J Biol Chem 1996, 271, 16237-16244.
Margineanu DG, Klitgaard H: Diff erential eff ects of cation-chloride co-transport-blocking diuretics in a rat hippocampal slice model of epilepsy. Epilepsy Res 2006, 69, 93-99.
Reid KH, Li G-Y, Payne RS, Schurr A, Cooper NGF: The mRNA level of the potassium-chloride co-transporter KCC2 covaries with seizure susceptibility in inferior colliculus of the post-ischemic audiogenic seizure-prone rat. Neurosci Lett 2001, 308, 29-32.
Dalby NO, Nielsen E B: Comparison of the preclinical anticonvulsant profi les of tiagabine, lamotrigine, gabapentin and vigabatrin. Epilepsy Res 1997, 28, 63-72.
Loscher W, Fassbender CP, Nolting B: The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. II. Maximal electroshock seizure models. Epilepsy Res 1991, 8, 79-94.
Litchfi eld JT, Wilcoxon F: A simplifi ed method of evaluating dose-eff ect experiments. J Pharmacol Exp Ther 1949, 96, 99-113.
Łuszczki JJ, Borowicz KK, Swiąder M, Czuczwar SJ: Interactions between oxcarbazepine and conventional antiepileptic drugs in the maximal electroshock test in mice: an isobolographic analysis. Epilepsia 2003, 44, 489-499.
Czuczwar SJ, Patsalos PN: The new generation of GABA enhancers. CNS Drugs 2001, 15, 339-350.
Suzdak PD, Jansen JA: A review of the preclinical pharmacology of tiagabine: a potent and selective anticonvulsant GABA uptake inhibitor. Epilepsia 1995, 36, 612-626.
Łuszczki JJ, Czuczwar SJ: Isobolographic profi le of interactions between tiagabine and gabapentin: a preclinical study. Naunyn Schmiedeberg Arch Pharmacol 2004, 369, 434-446.
White HS, Brown SD, Woodhead JH, Skeen GA, Wolf HH: Topiramate modulates GABA-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism. Epilepsia 2000, 41(Suppl 1), S17-S20.
Loscher W: Basic Pharmacology of Valproate. CNS Drugs 2002, 10, 669-694.
Twyman RE, Rogers CJ, Macdonald RL: Diff erential regulation of γ-aminobutyric acid receptor channels by diazepam and phenobarbital. Ann Neurol 1989, 25, 213-220.
Journals System - logo
Scroll to top