Nicorandil repurposing in orofacial pain: preclinical findings in adult zebrafish.

IF 3.6 4区 医学 Q2 CHEMISTRY, MEDICINAL
ChemMedChem Pub Date : 2025-03-22 DOI:10.1002/cmdc.202401007
José Ismael de Araújo, Gerlânia Leite, Leonardo da Silva-Neto, Antonio Eufrásio Vieira-Neto, Angelo de Fátima, Adriana Rolim Campos
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引用次数: 0

Abstract

This study investigated the orofacial antinociceptive activity of nicorandil in adult zebrafish and explored the involvement of TRP channels in this effect. Nicorandil, a known antianginal drug, reduced nociceptive behaviors induced by capsaicin (TRPV1 agonist), cinnamaldehyde (TRPA1 agonist), and menthol (TRPM8 agonist) without altering the locomotor activity of the zebrafish. Pre-treatment with specific TRPA1 and TRPV1 antagonists prevented the antinociceptive effects of nicorandil, indicating its action on these channels. Molecular docking studies supported these findings, demonstrating high chemical affinity and specific binding of nicorandil to the TRPV1 and TRPA1 channels, leading to stabilization and reduced biological activity of these channels. In contrast, the antinociceptive effect of nicorandil on menthol-induced nociception was not affected by a TRPM8 antagonist, suggesting that TRPM8 modulation is not involved in nicorandil's mechanism of action. The study highlights the potential of nicorandil as an analgesic through its interaction with TRPV1 and TRPA1 channels, providing a molecular basis for repositioning nicorandil as an effective analgesic drug.

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来源期刊
ChemMedChem
ChemMedChem 医学-药学
CiteScore
6.70
自引率
2.90%
发文量
280
审稿时长
1 months
期刊介绍: Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.
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