African Journal of
Pharmacy and Pharmacology

  • Abbreviation: Afr. J. Pharm. Pharmacol.
  • Language: English
  • ISSN: 1996-0816
  • DOI: 10.5897/AJPP
  • Start Year: 2007
  • Published Articles: 2121

Full Length Research Paper

Involvement of pro-inflammatory cytokines and nociceptive pathways on the pharmacological activity of hydantoin derivative 5-(4-isopropylphenyl)-3-phenyl-imidazolidine-2,4-dione

Fabíola Lélis de Carvalho
  • Fabíola Lélis de Carvalho
  • Laboratório de Psicofarmacologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba (UFPB), João Pessoa, PB, 58051-900, Brazil.
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Diogo Vilar da Fonsêca
  • Diogo Vilar da Fonsêca
  • Laboratório de Psicofarmacologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba (UFPB), João Pessoa, PB, 58051-900, Brazil.
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Antônia Rosangela Soares Penha
  • Antônia Rosangela Soares Penha
  • Laboratório de Psicofarmacologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba (UFPB), João Pessoa, PB, 58051-900, Brazil.
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Mirian Graciela da Silva Stiebbe Salvadori
  • Mirian Graciela da Silva Stiebbe Salvadori
  • Laboratório de Psicofarmacologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba (UFPB), João Pessoa, PB, 58051-900, Brazil.
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Paula Regina Rodrigues Salgado
  • Paula Regina Rodrigues Salgado
  • Laboratório de Psicofarmacologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba (UFPB), João Pessoa, PB, 58051-900, Brazil.
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Charlane Kelly Souto Pereira
  • Charlane Kelly Souto Pereira
  • Laboratório de Psicofarmacologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba (UFPB), João Pessoa, PB, 58051-900, Brazil.
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Fagner Carvalho Leite
  • Fagner Carvalho Leite
  • Laboratório de Imunologia, Centro de Ciências da Saúde, UFPB, João Pessoa, PB, 58051-900, Brazil.
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Márcia Regina Piuvezam
  • Márcia Regina Piuvezam
  • Laboratório de Psicofarmacologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba (UFPB), João Pessoa, PB, 58051-900, Brazil.
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Severino Araújo de Sousa
  • Severino Araújo de Sousa
  • Laboratório de Química Orgânica, Departamento de Química, UFPB, João Pessoa, PB, 58051-900, Brazil.
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Petrônio Filgueiras de Athayde-Filho
  • Petrônio Filgueiras de Athayde-Filho
  • Laboratório de Química Orgânica, Departamento de Química, UFPB, João Pessoa, PB, 58051-900, Brazil.
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Liana Clébia de Morais Pordeus
  • Liana Clébia de Morais Pordeus
  • Laboratório de Psicofarmacologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba (UFPB), João Pessoa, PB, 58051-900, Brazil.
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Reinaldo Nóbrega de Almeida
  • Reinaldo Nóbrega de Almeida
  • Laboratório de Psicofarmacologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba (UFPB), João Pessoa, PB, 58051-900, Brazil.
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  •  Received: 08 September 2016
  •  Accepted: 19 September 2016
  •  Published: 30 September 2016

Abstract

Hydantoins are often reported as potent anticonvulsant drugs; however, recent studies have highlighted their antinociceptive potential. Based on these reports, this study investigated the antinociceptive and anti-inflammatory activities of the hydantoin derivative 5-(4-isopropylphenyl)-3-phenyl-imidazolidine-2,4-dione (IM-7) using animal models. Treated mice submitted to the acetic acid-induced writhing test showed increase (p<0.01 or p<0.001) in the latency to the first writhing and reduction in the number of abdominal writhing (p<0.001). Furthermore, all doses reduced the nociceptive response in the first (p<0.05 or p<0.001) and second (p<0.001) phases of the formalin test. This effect was inhibited by pretreatment with the antagonists naloxone, sulpiride and caffeine. Additionally, IM-7 (75, 150 and 300 mg/kg, i.p.) reduced (p<0.05 or p<0.001) the glutamate-induced nociceptive response. Carrageenan-induced paw edema was strongly reduced following treatment with all doses of IM-7 (p<0.05, p<0.01 or p<0.001), and so were leukocyte migration and levels of interleukin-1β (300 mg/kg: p<0.001) and tumor necrosis factor-α (300 mg/kg: p<0.01) in carrageenan-induced peritonitis. Therefore, IM-7 decreased the nociceptive response via a mechanism involving the opioid, dopaminergic, and adenosinergic receptors. Its anti-inflammatory action also contributed by decreasing the release of pro-inflammatory cytokines.

Key words: Pain, inflammation, IM-7, nociception.