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

• Autorzy: Jarogniew J. Luszczki , Magdalena Leszkowicz , Maria W. Kondrat-Wrobel , Magdalena Florek-Luszczki
• 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.

Słowa kluczowe

EN

SYM 2206; threshold for maximal electroshock-induced seizures; TID20; TID50; mice.

• Czasopismo: Current Issues in Pharmacy and Medical Sciences
• Rocznik: 2014
• Tom: 27
• Numer: 2
• Strony: 80-83

Daty

wydano

2014-06-01

otrzymano

2014-03-26

zaakceptowano

2014-05-27

online

2014-11-25

Twórcy

autor

Jarogniew J. Luszczki

• Department of Pathophysiology, Medical University of Lublin, Ceramiczna 1, 20-150 Lublin, Poland,
• Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, 20-950 Lublin, Poland

autor

Magdalena Leszkowicz

• Department of Pathophysiology, Medical University of Lublin, Ceramiczna 1, 20-150 Lublin, Poland

autor

Maria W. Kondrat-Wrobel

• Department of Pathophysiology, Medical University of Lublin, Ceramiczna 1, 20-150 Lublin, Poland

autor

Magdalena Florek-Luszczki

• Department of Public Health, Institute of Rural Health, Jaczewskiego 2, 20-950 Lublin, Poland

Bibliografia

• 1. Behr J. et al.: Kindling enhances kainite receptor-mediated depression of GABAergic inhibition in rat granule cells. Eur. J. Neurosci., 16, 861, 2002.
• 2. Ghersi C. et al.: Pharmacological heterogeneity of release-regulating presynaptic AMPA/kainate receptors in the rat brain: study with receptor antagonists. Neurochem. Int., 42, 283, 2003.
• 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.
• 5. Litchfield J.T., Wilcoxon F.: A simplified method of evaluating doseeffect experiments. J. Pharmacol. Exp. Ther., 96, 99, 1949.
• 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]
• 13. Łuszczki J.J. et al.: Stiripentol in a dose-dependent manner elevates the threshold for maximal electroshock-induced seizures in mice. J. Pre-Clin. Clin. Res., 1, 155, 2007.
• 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.
• 17. Swinyard E.A., Brown W.C., Goodman L.S.: Comparative assays of antiepileptic drugs in mice and rats. J. Pharmacol. Exp. Ther., 106, 319, 1952.
• 18. Welch N.C. et al.: Traditional AMPA receptor antagonists partially block Na v1.6-mediated persistent current. Neuropharmacology, 55, 1165, 2008. [WoS]

Identyfikatory

DOI

10.2478/cipms-2014-0018