ISOBOLOGRAPHIC ASSESSMENT OF INTERACTIONS BETWEEN RETIGABINE AND PHENYTOIN IN THE MOUSE MAXIMAL ELECTROSHOCK-INDUCED SEIZURE MODEL AND CHIMNEY TEST

Dorota Żółkowska; Mirosław Zagaja; Barbara Miziak; Maria W. Kondrat-Wróbel; Katarzyna Załuska; Magdalena Florek-Łuszczki; Monika Szpringer; Bartłomiej Drop; Marek Zadrożniak; Stanisław Czuczwar; Jarogniew J. Łuszczki

doi:10.5114/hpc.2016.63572

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Original paper

ISOBOLOGRAPHIC ASSESSMENT OF INTERACTIONS BETWEEN RETIGABINE AND PHENYTOIN IN THE MOUSE MAXIMAL ELECTROSHOCK-INDUCED SEIZURE MODEL AND CHIMNEY TEST

Dorota Żółkowska

¹

,

Mirosław Zagaja

²

,

Barbara Miziak

³

,

Maria W. Kondrat-Wróbel

³

,

Katarzyna Załuska

³

,

Magdalena Florek-Łuszczki

⁴

,

Monika Szpringer

⁵

,

Bartłomiej Drop

³

,

Marek Zadrożniak

⁶

,

Stanisław J. Czuczwar

³

,

Jarogniew J. Łuszczki

³

University of California Davis School of Medicine, Sacramento, United States of America

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

Medical University of Lublin, Department of Pathophysiology, Poland

Institute of Rural Health, Centre of Public Health and Health Promotion, Lublin, Poland

The Jan Kochanowski University in Kielce, Faculty of Medicine and Health Sciences, Poland

Medical University of Lublin, Department of Otolaryngology, Poland

Health Problems of Civilization. 2016; 10(4): 54-59

DOI: https://doi.org/10.5114/hpc.2016.63572

Online publish date: 2016/12/13

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AMA

Żółkowska D, Zagaja M, Miziak B, et al. ISOBOLOGRAPHIC ASSESSMENT OF INTERACTIONS BETWEEN RETIGABINE AND PHENYTOIN IN THE MOUSE MAXIMAL ELECTROSHOCK-INDUCED SEIZURE MODEL AND CHIMNEY TEST. Health Problems of Civilization. 2016;10(4):54-59. doi:10.5114/hpc.2016.63572.

APA

Żółkowska, D., Zagaja, M., Miziak, B., Kondrat-Wróbel, M., Załuska, K.,  & Florek-Łuszczki, M. et al. (2016). ISOBOLOGRAPHIC ASSESSMENT OF INTERACTIONS BETWEEN RETIGABINE AND PHENYTOIN IN THE MOUSE MAXIMAL ELECTROSHOCK-INDUCED SEIZURE MODEL AND CHIMNEY TEST. Health Problems of Civilization, 10(4), 54-59. https://doi.org/10.5114/hpc.2016.63572

Chicago

Żółkowska, Dorota, Mirosław Zagaja, Barbara Miziak, Maria W. Kondrat-Wróbel, Katarzyna Załuska, Magdalena Florek-Łuszczki,  and Monika Szpringer et al. 2016. "ISOBOLOGRAPHIC ASSESSMENT OF INTERACTIONS BETWEEN RETIGABINE AND PHENYTOIN IN THE MOUSE MAXIMAL ELECTROSHOCK-INDUCED SEIZURE MODEL AND CHIMNEY TEST". Health Problems of Civilization 10 (4): 54-59. doi:10.5114/hpc.2016.63572.

Harvard

Żółkowska, D., Zagaja, M., Miziak, B., Kondrat-Wróbel, M., Załuska, K., Florek-Łuszczki, M., Szpringer, M., Drop, B., Zadrożniak, M., Czuczwar, S.,  and Łuszczki, J. (2016). ISOBOLOGRAPHIC ASSESSMENT OF INTERACTIONS BETWEEN RETIGABINE AND PHENYTOIN IN THE MOUSE MAXIMAL ELECTROSHOCK-INDUCED SEIZURE MODEL AND CHIMNEY TEST. Health Problems of Civilization, 10(4), pp.54-59. https://doi.org/10.5114/hpc.2016.63572

MLA

Żółkowska, Dorota et al. "ISOBOLOGRAPHIC ASSESSMENT OF INTERACTIONS BETWEEN RETIGABINE AND PHENYTOIN IN THE MOUSE MAXIMAL ELECTROSHOCK-INDUCED SEIZURE MODEL AND CHIMNEY TEST." Health Problems of Civilization, vol. 10, no. 4, 2016, pp. 54-59. doi:10.5114/hpc.2016.63572.

Vancouver

Żółkowska D, Zagaja M, Miziak B, Kondrat-Wróbel M, Załuska K, Florek-Łuszczki M et al. ISOBOLOGRAPHIC ASSESSMENT OF INTERACTIONS BETWEEN RETIGABINE AND PHENYTOIN IN THE MOUSE MAXIMAL ELECTROSHOCK-INDUCED SEIZURE MODEL AND CHIMNEY TEST. Health Problems of Civilization. 2016;10(4):54-59. doi:10.5114/hpc.2016.63572.

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Background. Search for beneficial combinations of antiepileptic drugs (AEDs) that can be used in patients with pharmacoresistant epilepsy, is still conducted both empirically and rationally, based on molecular mechanisms of AEDs’ action. This study was aimed at characterizing the interaction profiles for the combination of two AEDs (i.e., retigabine [RTG] and phenytoin [PHT]) in the maximal electroshock-induced seizures (MES) and chimney test (motor performance) in adult male albino Swiss mice.

Material and methods. Type I isobolographic analysis was used to determine interactions for the combination of RTG with PHT (at three fixed-ratios of 1:3, 1:1 and 3:1) with respect to its anticonvulsant and acute neurotoxic effects in the MES and chimney tests, respectively. Total brain concentrations of RTG and PHT were estimated to exclude any pharmacokinetic interaction between AEDs.

Results. The combination of RTG with PHT at the fixed-ratios of 1:3, 1:1 and 3:1 produced additive interactions in both, the MES and chimney tests. RTG and PHT did not affect each other their total brain concentrations in mice, confirming pharmacodynamic interaction between the investigated drugs. Conclusions. The combination of RTG with PHT was neutral

suggesting that this two-drug combination might occur favorable in some patients with refractory epilepsy.

keywords:

ISOBOLOGRAPHIC ASSESSMENT OF INTERACTIONS BETWEEN RETIGABINE AND PHENYTOIN IN THE MOUSE MAXIMAL ELECTROSHOCK-INDUCED SEIZURE MODEL AND CHIMNEY TEST

Dorota Żółkowska 1 , Mirosław Zagaja 2 , Barbara Miziak 3 , Maria W. Kondrat-Wróbel 3 , Katarzyna Załuska 3 , Magdalena Florek-Łuszczki 4 , Monika Szpringer 5 , Bartłomiej Drop 3 , Marek Zadrożniak 6 , Stanisław J. Czuczwar 3 , Jarogniew J. Łuszczki 3

drug interactions, isobolographic analysis, phenytoin, retigabine