PURPOSE: A series of delta-valerolactones has been synthesized in good yields, by reaction of ethyl acetoacetate with several aldehydes in presence of LDA. METHODS AND RESULTS: The in vivo analgesic activity of these compounds has been evaluated. The results indicate that the lactones synthesized showed an important antinociceptive effect at 10 mg/kg, administered intraperitoneally in mice, which significantly inhibited the abdominal constrictions induced by acetic acid when compared to acetylsalicylic acid and acetaminophen in the same dose, and increased significantly the thermal sensibility at the hot-plate method, although they were less effective than morphine in the same assay. CONCLUSIONS: The antinociceptive models employed here reveal a potential analgesic effect of the delta-valerolactones synthesized. Further investigations are needed to discern which mechanism of action is concern.
PURPOSE: A series of delta-valerolactones has been synthesized in good yields, by reaction of ethyl acetoacetate with several aldehydes in presence of LDA. METHODS AND RESULTS: The in vivo analgesic activity of these compounds has been evaluated. The results indicate that the lactones synthesized showed an important antinociceptive effect at 10 mg/kg, administered intraperitoneally in mice, which significantly inhibited the abdominal constrictions induced by acetic acid when compared to acetylsalicylic acid and acetaminophen in the same dose, and increased significantly the thermal sensibility at the hot-plate method, although they were less effective than morphine in the same assay. CONCLUSIONS: The antinociceptive models employed here reveal a potential analgesic effect of the delta-valerolactones synthesized. Further investigations are needed to discern which mechanism of action is concern.