Antinociceptive Effect of 7-hydroxy-3,4-dihydrocadalin Isolated from Heterotheca inuloides: Role of Peripheral 5-HT1 Serotonergic Receptors

The purpose of this study was to investigate the antinociceptive effect of Heterotheca inuloides in inflammatory pain and to identify the main compounds involved in this effect. In the formalin tests, the n-hexane extract was the most potent extract (ED₃₀=70.5±18.7µg/paw and 64.6±30.1µg/paw for the phase 1 and 2, respectively), followed by dichloromethane (ED₃₀=289.4±71.1µg/paw and 640.6±182.0µg/paw), ethyl acetate (ED₃₀=352.4±90.6µg/paw and 628.4±163.8µg/paw) and methanol (not active). Bio-guided fractionation of the n-hexane extract lead to identify 7-hydroxy-3,4-dihydrocadalin (1) as one of the active antinociceptive compounds. This compound was equipotent to (ED₃₀=76.5±24.1µg/paw) and equieffective (45.6±8.8%) with diclofenac (ED₃₀=59.6±7.0µg/paw and 44.8±3.1%) in phase 2 of the formalin test, but it was more potent (ED₃₀=73.8±29.5µg/paw) and effective (45.6±7.1%) than diclofenac (ED₃₀=no effect and 9.0±11.3%) in phase 1. The antinociceptive effect of 1 (100µg/paw) was significantly prevented by methiothepin (30µg/paw), WAY100635 (0.3µg/paw); SB224289 (30µg/paw) and BRL15572 (30µg/paw) but not by naltrexone (30µg/paw) in both phases of the formalin test. These data suggest that antinociceptive effect of 1 occurs through activation of 5-HT₁ receptors[1].

Acknowledgements: This work was supported by grant of Dirección General de Asuntos del Personal Académico DGAPA-UNAM IN 210910 and CONACYT 82613. H. Rocha-González is a DGAPA-UNAM postdoctoral fellowship.

References: [1] Rocha-González HI, Blaisdell-López E, Granados-Soto V, Navarrete A. (2010) Euro J Pharmacol, 649: 154–160.