Chronic oral toxicity studies of nefopam hydrochloride in rats and dogs

Abstract Nefopam hydrochloride, a new non-narcotic analgesic agent, was evaluated for chronic oral toxicity in several rat and dog experiments. Rats were given 20, 40, and 160 mg/kg/day for 6 months and 1 yr; dogs received the drug at dosages of 20, 40, and 80 mg/kg/day for 6 months and 1 yr. The treated rats had a dose-related reduction in body weight and the male rats had dose-related liver changes (increased relative weight, pale gross appearance, and microscopic fatty changes). The dogs did not exhibit body weight or liver changes, but in the 1-yr study central nervous system stimulation (excited behavior and sporadic convulsions) was seen at the higher two dose levels.