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2014 | 27 | 2 | 80-83
Tytuł artykułu

SYM 2206 (a potent non-competitive AMPA receptor antagonist) elevates the threshold for maximal electroshock-induced seizures in mice

Treść / Zawartość
Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
The aim of this study was to determine the effect of SYM 2206 (a potent non-competitive AMPA receptor antagonist) on the threshold for maximal electroshock (MEST)-induced seizures in mice. Electroconvulsions were produced in mice by means of a current (sinewave, 50 Hz, maximum 500 V, strength from 4 to 14 mA, 0.2-s stimulus duration, tonic hind limb extension taken as the endpoint) delivered via ear-clip electrodes. SYM 2206 administered systemically (i.p.), 30 min before the MEST test, at doses of 2.5 and 5 mg/kg, did not alter the threshold for maximal electroconvulsions in mice. In contrast, SYM 2206 at doses of 10 and 20 mg/kg significantly elevated the threshold for maximal electroconvulsions in mice (P<0.01 and P<0.001). Linear regression analysis of SYM 2206 doses and their corresponding threshold increases allowed for the determination of threshold increasing doses by 20% and 50% (TID20 and TID50 values) that elevate the threshold in drug-treated animals over the threshold in control animals. The experimentally derived TID20 and TID50 values for SYM 2206 were 4.25 and 10.56 mg/kg, respectively. SYM 2206 dose-dependently increased the threshold for MEST-induced seizures, suggesting the anticonvulsant action of the compound in this seizure model in mice.
Wydawca

Rocznik
Tom
27
Numer
2
Strony
80-83
Opis fizyczny
Daty
wydano
2014-06-01
otrzymano
2014-03-26
zaakceptowano
2014-05-27
online
2014-11-25
Twórcy
  • Department of Pathophysiology, Medical University of Lublin, Ceramiczna 1, 20-150 Lublin, Poland, jarogniew.luszczki@gmail.com
  • Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, 20-950 Lublin, Poland
  • Department of Pathophysiology, Medical University of Lublin, Ceramiczna 1, 20-150 Lublin, Poland
  • Department of Pathophysiology, Medical University of Lublin, Ceramiczna 1, 20-150 Lublin, Poland
  • Department of Public Health, Institute of Rural Health, Jaczewskiego 2, 20-950 Lublin, Poland
Bibliografia
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  • 3. Glantz S.A., Slinker B.K.: editors (2001). Primer of applied regression and analysis of variance, second edition. McGraw-Hill Inc.: New York, NY.
  • 4. Krauss G.L.: Perampanel: a selective AMPA antagonist for treating seizures. Epilepsy Curr., 13, 269, 2013.
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  • 6. Löscher W., Fassbender C.P., Nolting B.: The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. II. Maximal electroshock seizure models. Epilepsy Res., 8, 79, 1991.
  • 7. Löscher W., Wauquier A.: Use of animal models in developing guiding principles for polypharmacy in epilepsy. Epilepsy Res., Suppl. 11, 61, 1996.
  • 8. Łuszczki J.J., Antkiewicz-Michaluk L., Czuczwar S.J.: Isobolographic analysis of interactions between 1-methyl-1,2,3,4-tetrahydroisoquinoline and four conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model. Eur. J. Pharmacol., 602, 298, 2009.[WoS]
  • 9. Łuszczki J.J., Czuczwar S.J.: How significant is the difference between drug doses influencing the threshold for electroconvulsions? Pharmacol. Rep., 57, 782, 2005.
  • 10. Łuszczki J.J., Czuczwar S.J.: Isobolographic characterization of interactions between vigabatrin and tiagabine in two experimental models of epilepsy. Prog. Neuropsychopharmacol. Biol. Psychiatry, 31, 529, 2007.
  • 11. Łuszczki J.J. et al.: Isobolographic analysis of interactions between loreclezole and conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model. Naunyn- Schmiedebergs Arch. Pharmacol., 373, 169, 2006.
  • 12. Łuszczki J.J. et al.: Isobolographic and behavioral characterizations of interactions between vigabatrin and gabapentin in two experimental models of epilepsy. Eur. J. Pharmacol., 595, 13, 2008.[WoS]
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  • 14. Pelletier J.C. et al.: Substituted 1,2-dihydrophthalazines: potent, selective, and noncompetitive inhibitors of the AMPA receptor. J. Med. Chem., 39, 343, 1996.
  • 15. Rogawski M.A.: AMPA receptors as a molecular target in epilepsy therapy. Acta Neurol. Scand. Suppl., 197, 9, 2013.
  • 16. Rogawski M.A., Donevan S.D.: AMPA receptors in epilepsy and as targets for antiepileptic drugs. Adv. Neurol., 79, 947, 1999.
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  • 18. Welch N.C. et al.: Traditional AMPA receptor antagonists partially block Na v1.6-mediated persistent current. Neuropharmacology, 55, 1165, 2008. [WoS]
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.-psjd-doi-10_2478_cipms-2014-0018
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