title: Evidence for the involvement of descending pain-inhibitory mechanisms in the antinociceptive effect of hecogenin acetate.
abstract: 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 mechanisms.
authors: Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BA, CEP 40170-290, Brazil.
authors: Kelly Barbosa
authors: KB
authors: Gama
authors: Jullyana S S
authors: JS
authors: Quintans
authors: Angelo R
authors: AR
authors: Antoniolli
authors: Lucindo J
authors: LJ
authors: Quintans-Júnior
authors: Wagno Alcântara
authors: WA
authors: Santana
authors: Alexsandro
authors: A
authors: Branco
authors: Milena Botelho Pereira
authors: MB
authors: Soares
authors: Cristiane Flora
authors: CF
authors: Villarreal
mesh_terms: D027882:Agave / Q000737:chemistry*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D005905:Glyburide / Q000494:pharmacology; D054086:KATP Channels / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009271:Naltrexone / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D010487:Periaqueductal Gray / Q000187:drug effects; D018515:Plant Leaves / Q000737:chemistry; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D013141:Spiro Compounds / Q000494:pharmacology*; D013256:Steroids / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D054086:KATP Channels; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013141:Spiro Compounds; D013256:Steroids; C505698:hecogenin acetate; D009271:Naltrexone; D005905:Glyburide