Synthesis, antinociceptive activity and pharmacokinetic profiles of nicorandil and its isomers
| Autor: | Julliana Ribeiro Alves Santos, Adriana M. Godin, Gerson Antônio Pianetti, Francinely C. Oliveira, Márcio M. Coelho, Débora P. Araújo, Renes R. Machado, Mariana O. Almeida, Raquel R. Menezes, Ângelo de Fátima, Marcela M.G.B. Dutra, Isabela Costa César, Daniel Assis Santos |
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| Rok vydání: | 2014 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Pain Pharmaceutical Science Vasodilation Pharmacology Biochemistry Nitric oxide Mice chemistry.chemical_compound Isomerism Pharmacokinetics Drug Discovery medicine Animals Nitrite Nicorandil Molecular Biology Analgesics Nicotinamide Organic Chemistry Disease Models Animal Nociception chemistry cardiovascular system Molecular Medicine Female Half-Life medicine.drug Guanylate cyclase |
| Zdroj: | Bioorganic & Medicinal Chemistry. 22:2783-2790 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2014.03.011 |
| Popis: | Nicorandil (N-(2-hydroxyethyl)nicotinamide nitrate) is an antianginal drug, which activates guanylyl cyclase and opens the ATP-dependent K(+) channels, actions that have been suggested to mediate its vasodilator activity. We synthesized nicorandil and its two isomers, which vary in the positions of the side chain containing the nitric oxide (NO) donor, and also their corresponding denitrated metabolites. The activities of these compounds were evaluated in an experimental model of pain in mice. Pharmacokinetic parameters of nicorandil and its isomers, as well as the plasma concentrations of the corresponding denitrated metabolites and also nicotinamide and nitrite were determined. Nicorandil exhibited the highest antinociceptive activity, while the ortho-isomer was the least active. Nicorandil and para-nicorandil, which induced higher plasma concentrations of nitrite, exhibited higher antinociceptive activity, which suggests that the release of NO may mediate this activity. |
| Databáze: | OpenAIRE |
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