Evaluation of analgesic activity and toxicity of alkaloids in Myristica fragrans seeds in mice

Aim: To examine the analgesic effect of alkaloids in Myristica fragrans seed in a mouse model of acetic acid-induced visceral pain. Methods: Alkaloids were extracted from ground nutmeg seed kernels with 10% acetic acid in 95% ethyl alcohol. Visceral pain was induced in male and female BALB/c mice by intraperitoneal injection of 0.6% acetic acid. Analgesic effect of alkaloids (0.5 gram or 1 gram per kilogram [g/kg], by mouth) was assessed by evaluating writhing response. Acute toxicity was tested in response to 2, 3, 4, 5, or 6 g/kg of alkaloid extract; the median lethal dose (LD50) was determined by probit analysis. Results: Alkaloid extract at a dose of 1 g/kg significantly reduced the number of writhing responses in female, but not male mice; 0.5 g/kg of alkaloid extract had no effect in either sex. The LD50 was 5.1 g/kg. Signs of abnormal behavior, including hypoactivity, unstable gait, and dizziness were seen in animals given a dose of 4 g/kg or higher; abnormal behavior lasted for several hours after administration of the alkaloids. Conclusion: According to the classification of Loomis and Hayes, M. fragrans seed alkaloids have analgesic activity and are slightly toxic.