Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 5, May, p. 609–613

doi: 10.17219/acem/68694

Publication type: original article

Language: English

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Comparison of the anticonvulsant potency of various diuretic drugs in the maximal electroshock-induced seizure threshold test in mice

Katarzyna Załuska1,B,C,D, Maria W. Kondrat-Wróbel1,B,C,D, Jarogniew J. Łuszczki1,2,A,C,D,E,F

1 Department of Pathophysiology, Medical University of Lublin, Poland

2 Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, Poland

Abstract

Background. The coexistence of seizures and arterial hypertension requires an adequate and efficacious treatment involving both protection from seizures and reduction of high arterial blood pressure. Accumulating evidence indicates that some diuretic drugs (with a well-established position in the treatment of arterial hypertension) also possess anticonvulsant properties in various experimental models of epilepsy.
Objectives. The aim of this study was to assess the anticonvulsant potency of 6 commonly used diuretic drugs (i.e., amiloride, ethacrynic acid, furosemide, hydrochlorothiazide, indapamide, and spironolactone) in the maximal electroshock-induced seizure threshold (MEST) test in mice.
Material and Methods. Doses of the studied diuretics and their corresponding threshold increases were linearly related, allowing for the determination of doses which increase the threshold for electroconvulsions in drug-treated animals by 20% (TID20 values) over the threshold in control animals.
Results. Amiloride, hydrochlorothiazide and indapamide administered systemically (intraperitoneally – i.p.) increased the threshold for maximal electroconvulsions in mice, and the experimentally-derived TID20 values in the maximal electroshock seizure threshold test were 30.2 mg/kg for amiloride, 68.2 mg/kg for hydrochlorothiazide and 3.9 mg/kg for indapamide. In contrast, ethacrynic acid (up to 100 mg/kg), furosemide (up to 100 mg/kg) and spironolactone (up to 50 mg/kg) administered i.p. had no significant impact on the threshold for electroconvulsions in mice.
Conclusion. The studied diuretics can be arranged with respect to their anticonvulsant potency in the MEST test as follows: indapamide > amiloride > hydrochlorothiazide. No anticonvulsant effects were observed for ethacrynic acid, furosemide or spironolactone in the MEST test in mice.

Key words

diuretic drugs, threshold for electroconvulsions, TID20 values

References (24)

  1. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: Analysis of worldwide data. Lancet. 2005;365:217–223.
  2. Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy. N Engl J Med. 2011;365:919–926.
  3. Patsalos PN, Froscher W, Pisani F, van Rijn CM. The importance of drug interactions in epilepsy therapy. Epilepsia. 2002;43:365–385.
  4. Doroszko A, Janus A, Szahidewicz-Krupska E, Mazur G, Derkacz A. Resistant hypertension. Adv Clin Exp Med. 2016;25:173–183.
  5. Ali A, Ahmad FJ, Dua Y, Pillai KK, Vohora D. Seizures and sodium hydrogen exchangers: Potential of sodium hydrogen exchanger inhibitors as novel anticonvulsants. CNS Neurol Disord Drug Targets. 2008;7:343–347.
  6. Kahle KT, Staley KJ. The bumetanide-sensitive Na-K-2Cl cotransporter NKCC1 as a potential target of a novel mechanism-based treatment strategy for neonatal seizures. Neurosurg Focus. 2008;25:E22. doi:10.3171/FOC/2008/25/9/E22
  7. Löscher W, Puskarjov M, Kaila K. Cation-chloride cotransporters NKCC1 and KCC2 as potential targets for novel antiepileptic and antiepileptogenic treatments. Neuropharmacology. 2013;69:62–74.
  8. Xiong ZG, Pignataro G, Li M, Chang SY, Simon RP. Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases. Curr Opin Pharmacol. 2008;8:25–32.
  9. Luszczki JJ, Sawicka KM, Kozinska J, Dudra-Jastrzebska M, Czuczwar SJ. Amiloride enhances the anticonvulsant action of various antiepileptic drugs in the mouse maximal electroshock seizure model. J Neural Transm. 2009;116:57–66.
  10. Lukawski K, Swiderska G, Czuczwar SJ. Effect of hydrochlorothiazide on the anticonvulsant action of antiepileptic drugs against maximal electroshock-induced seizures in mice. Pharmacol Rep. 2012;64:315–320.
  11. Kozinska J, Sawicka KM, Zadrozniak A, et al. Indapamide enhances the protective action of carbamazepine, phenobarbital, and valproate against maximal electroshock-induced seizures in mice. Adv Med Sci. 2009;54:66–74.
  12. Swinyard EA, Brown WC, Goodman LS. Comparative assays of antiepileptic drugs in mice and rats. J Pharmacol Exp Ther. 1952;106:319–330.
  13. Löscher 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.
  14. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington, DC: National Academies Press US; 2011.
  15. Kondrat-Wróbel MW, Luszczki JJ. Interaction of three-drug combination of lacosamide, carbamazepine and phenobarbital in the mouse maximal electroshock-induced seizure model: An isobolographic analysis. Health Probl Civiliz. 2016;10:55–61.
  16. Litchfield JT Jr, Wilcoxon F. A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther. 1949;96:99–113.
  17. Luszczki JJ, Czuczwar SJ. Isobolographic characterization of interactions between vigabatrin and tiagabine in two experimental models of epilepsy. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:529–538.
  18. Luszczki JJ, Ratnaraj N, Patsalos PN, Czuczwar SJ. Isobolographic and behavioral characterizations of interactions between vigabatrin and gabapentin in two experimental models of epilepsy. Eur J Pharmacol. 2008;595:13–21.
  19. Luszczki JJ, Czuczwar SJ. How significant is the difference between drug doses influencing the threshold for electroconvulsions? Pharmacol Rep. 2005;57:782–786.
  20. Luszczki JJ, Dudra-Jastrzebska M, Andres-Mach M, et al. Stiripentol in a dose-dependent manner elevates the threshold for maximal electroshock-induced seizures in mice. JPCCR. 2007;1:155–157.
  21. Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 2008;22:659–661.
  22. Drugs.com. Indapamide dosage. http://www.drugs.com/dosage/indapamide.html. Updated August 5, 2016. Accessed March 6, 2018.
  23. Drugs.com. Amiloride dosage. http://www.drugs.com/dosage/amiloride.html. Updated March 8, 2016. Accessed March 6, 2018.
  24. Drugs.com. Hydrochlorothiazide dosage. http://www.drugs.com/dosage/hydrochlorothiazide.html. Updated August 9, 2016. Accessed March 6, 2018.