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• W2898867907 abstract "Novel agonist of α4β2* neuronal nicotinic receptor with antinociceptive efficacy in rodent models of acute and chronic pain Roberto T Sudo,1,2 Kenichiro Hayashida,3 Aluizio N Santos,2 Masahito Kawatani,3 Carlos ES Monteiro1 Roberto D Moreira,4 Margarete M Trachez,1 Guilherme C Montes,1 Gisele Zapata-Sudo1 1Program of Research in Drug Development of Biomedical Science, Institute of Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 2Post-Graduation Program in Medicine (General Surgery) of Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 3Department of Neurophysiology, Akita University School of Medicine, Akita, Japan; 4Cristalia Produtos Quimicos e Farmacêuticos Ltda, Itapira, São Paulo, Brazil. Objective: To demonstrate the antinociceptive and antihypersensitivity mechanisms of Cris-104 (1-{2-[5-(4-fluorophenyl)–1H-pyrazol-4-yl]ethyl}piperidine), a novel selective α4β2* nicotinic acetylcholine receptor (nAChR) agonist, in rodent acute/inflammatory and chronic pain models. Materials and methods: Hot-plate and formalin tests in mice were used to examine Cris-104-induced antinociceptive effects on thermal/inflammatory pain. Cris-104 effects on hypersensitivity, norepinephrine (NE) release in the spinal dorsal horn, and neuronal activity in the locus coeruleus (LC) were examined in rats with lumbar spinal nerve ligation using behavioral, microdialysis, and extracellular recording methods. Cris-104 effects on spontaneous locomotion were examined in an open-field test. Results: Cris-104 induced dose-dependent antinociception effects in hot-plate and formalin tests, and these effects were blocked by the general nAChR antagonist mecamylamine, the selective α4β2* nAChR antagonist dihydro-beta-erythroidine, and the α2-adrenoceptor antagonist yohimbine, but not by the α1-adrenoceptor antagonist prazosin. Systemic and spinally perfused Cris-104 increased NE concentrations in microdialysates from the spinal cord in both normal and SNL rats. Systemic Cris-104 increased neuronal activity in the LC of normal rats. Mecamylamine blocked the effects of Cris-104 on spinal NE release and LC neuronal activity. Systemic Cris-104 did not affect locomotor activity significantly. Conclusion: The α4β2 neuronal nAChR agonist, Cris-104, was effective for treatment of pain via descending noradrenergic inhibition of pain signaling. Keywords: pain, nicotinic receptor, Cris-104, epibatidine" @default.
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• W2898867907 date "2018-10-01" @default.
• W2898867907 modified "2023-10-16" @default.
• W2898867907 title "Novel agonist of &alpha;₄&beta;₂* neuronal nicotinic receptor with antinociceptive efficacy in rodent models of acute and chronic pain" @default.
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• W2898867907 doi "https://doi.org/10.2147/jpr.s169637" @default.
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