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Evidence for the involvement of descending pain-inhibitory mechanisms in the antinociceptive effect of hecogenin acetate.

By Kelly Barbosa Gama, Jullyana de Souza Siqueira Quintans, Angelo Roberto Antoniolli, Lucindo José Quintans Junior, Wagno Alcântara Santana, Alexsandro Branco, Milena Botelho Pereira Soares and Cristiane Flora Villarreal


Hecogenin is a sapogenin present in the leaves of species from the Agave genus, with a wide spectrum of reported pharmacological activities. The present study was undertaken to evaluate whether hecogenin acetate (1) has antinociceptive properties and to determine its mechanism of action. The nociceptive threshold was evaluated using the tail flick test in mice. Mice motor performance was evaluated in a Rotarod test. By using Fos expression as a marker of neural activation, the involvement of the periaqueductal gray in 1-induced antinociception was evaluated. Intraperitoneal administration of 1 (5−40 mg/kg) produced a dose-dependent increase in the tail flick latency time compared to vehicle-treated group (p < 0.01). Mice treated with 1 (40 mg/kg) did not show motor performance alterations. The antinociception of 1 (40 mg/kg) was prevented by naloxone (nonselective opioid receptor antagonist; 5 mg/kg), CTOP (μ-opioid receptor antagonist; 1 mg/kg), nor-BNI (κ- opioid receptor antagonist; 0.5 mg/kg), naltrindole (δ-opioid receptor antagonist; 3 mg/kg), or glibenclamide (ATP-sensitive K+ channel blocker; 2 mg/kg). Systemic administration of 1 (5−40 mg/kg) increased the number of Fos positive cells in the periaqueductal gray. The present study has demonstrated for the first time that 1 produces consistent antinociception mediated by opioid receptors and endogenous analgesic mechanism

Topics: Agave/química, Analgésicos/farmacologia, Dor/quimioterapia, Compostos de Espiro/farmacologia, Esteroides/farmacologia, Animais, Glibureto/farmacologia, Canais KATP/antagonistas & inibidores, Masculino, Camundongos, Estrutura Molecular, Naltrexona/farmacologia, Substância Cinzenta Periaquedutal/efeitos de drogas, Folhas de Planta/química, Receptores Opioides kappa/antagonistas & inibidores
Publisher: ACS Publications
Year: 2013
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