Use este identificador para citar ou linkar para este item: http://hdl.handle.net/1843/76034
Tipo: Artigo de Periódico
Título: Nicorandil inhibits mechanical allodynia induced by paclitaxel by activating opioidergic and serotonergic mechanisms
Autor(es): Marcela Ísis Morais
Márcio de Matos Coelho
Renes de Resende Machado
Felipe Fernandes Rodrigues
Sarah Olivia Alves Mendes da Costa
Franciele Aparecida Goulart
Fabio Campos Costa
Ivo Souza Ferraz de Melo
Paulo Sérgio de Almeida Augusto
Marcela de Moura Garcia Bini Dutra
Ângelo de Fátima
Resumo: Recently, we demonstrated that nicorandil exhibits activities in models of inflammatory and nociceptive pain. In the present study, we extended this investigation by evaluating the effects of nicorandil in models of neuropathic pain induced by paclitaxel or nerve injury in mice. Four intraperitoneal (i.p.) injections of paclitaxel (2 mg/kg.day, cumulative dose 8 mg/kg) or chronic constriction injury (CCI) of the sciatic nerve induced a long lasting mechanical allodynia. Per os (p.o.) administration of two doses of nicorandil (50, 100 and 150 mg/kg) on the 14th day after the first paclitaxel injection attenuated the mechanical allodynia. Equimolar doses of nicotinamide (86.7 mg/kg, p.o.) or nicotinic acid (87.7 mg/kg, p.o.) were devoid of effect. Mechanical allodynia induced by CCI was also attenuated by p.o. administration of two doses of nicorandil (150 mg/kg) on the 14th day after nerve injury. Nicorandil (50, 100 and 150 mg/kg, p.o.) did not affect motor activity. The antinociceptive activity of nicorandil in the model of mechanical allodynia induced by paclitaxel was partially attenuated by naltrexone (5 and 10 mg/kg, i.p.) or cyproheptadine (5 and 10 mg/kg, i.p.), but not by glibenclamide (20 and 40 mg/kg, p.o.). Concluding, nicorandil exhibits activity in experimental models of neuropathic pain when mechanical allodynia is fully established. Activation of opioidergic and serotonergic pathways mediates the antinociceptive activity of nicorandil. It is unlikely that this activity requires biotransformation to nicotinamide or nicotinic acid. Nicorandil should be further evaluated aiming to identify a new alternative in the pharmacological management of neuropathic pain.
Assunto: Dor
Farmacologia
Dor neuropática
Nicorandil
Paclitaxel
Ácido nicotínico
Doxorrubicina
Nicotinamida
Idioma: eng
País: Brasil
Editor: Universidade Federal de Minas Gerais
Sigla da Instituição: UFMG
Departamento: FAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS
ICX - DEPARTAMENTO DE QUÍMICA
Tipo de Acesso: Acesso Restrito
Identificador DOI: https://doi.org/10.1016/j.ejphar.2018.02.014
URI: http://hdl.handle.net/1843/76034
Data do documento: 2018
metadata.dc.url.externa: https://www.sciencedirect.com/science/article/pii/S001429991830089X
metadata.dc.relation.ispartof: European Journal of Pharmacology
Aparece nas coleções:Artigo de Periódico

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