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Effects of Agomelatine on Oxidative Stress in the Brain of Mice After Chemically Induced Seizures

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Abstract

Agomelatine is a novel antidepressant drug with melatonin receptor agonist and 5-HT(2C) receptor antagonist properties. We analyzed whether agomelatine has antioxidant properties. Antioxidant activity of agomelatine (25, 50, or 75 mg/kg, i.p.) or melatonin (50 mg/kg) was investigated by measuring lipid peroxidation levels, nitrite content, and catalase activities in the prefrontal cortex, striatum, and hippocampus of Swiss mice pentylenetetrazole (PTZ) (85 mg/kg, i.p.), pilocarpine (400 mg/kg, i.p.), picrotoxin (PTX) (7 mg/kg, i.p.), or strychnine (75 mg/kg, i.p.) induced seizure models. In the pilocarpine-induced seizure model, all dosages of agomelatine or melatonin showed a significant decrease in TBARS levels and nitrite content in all brain areas when compared to controls. In the strychnine-induced seizure model, all dosages of agomelatine and melatonin decreased TBARS levels in all brain areas, and agomelatine at low doses (25 or 50 mg/kg) and melatonin decreased nitrite contents, but only agomelatine at 25 or 50 mg/kg showed a significant increase in catalase activity in three brain areas when compared to controls. Neither melatonin nor agomelatine at any dose have shown no antioxidant effects on parameters of oxidative stress produced by PTX- or PTZ-induced seizure models when compared to controls. Our results suggest that agomelatine has antioxidant activity as shown in strychnine- or pilocarpine-induced seizure models.

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Acknowledgments

This research had financial support from the Brazilian National Research Council (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico.

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Authors and Affiliations

  1. School of Medicine, University of Fortaleza (UNIFOR)/RENORBIO, Rua Desembargador Floriano Benevides Magalhães, 221 3º Andar, Fortaleza, Ceará, 60811-690, Brazil

    Carlos Clayton Torres Aguiar

  2. Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo, 1127, Fortaleza, Ceará, 60430-270, Brazil

    Anália Barbosa Almeida, Paulo Victor Pontes Araújo, Germana Silva Vasconcelos, Edna Maria Camelo Chaves, Otoni Cardoso do Vale, Danielle Silveira Macêdo, Glauce Socorro de Barros Viana & Silvânia Maria Mendes Vasconcelos

  3. Department of Pharmacy, Faculty of Pharmacy, Odontology and Nursing, Federal University of Ceará, Rua Capitão Francisco Pedro 1210, Fortaleza, 60.431-327, Brazil

    Luzia Kalyne Almeida Moreira Leal

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  1. Carlos Clayton Torres Aguiar
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Correspondence to Silvânia Maria Mendes Vasconcelos.

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Aguiar, C.C.T., Almeida, A.B., Araújo, P.V.P. et al. Effects of Agomelatine on Oxidative Stress in the Brain of Mice After Chemically Induced Seizures. Cell Mol Neurobiol 33, 825–835 (2013). https://doi.org/10.1007/s10571-013-9949-0

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