The experimental toxicology of tramadol: an overview

The experimental toxicological findings of tramadol are reviewed and discussed. Tramadol is a centrally acting analgesic. In acute toxicity studies, LD50 values are estimated to be around 300-350 mg/kg body weight (rat, mouse, oral administration). After intravenous administration the LD50 values ranged from 50 to 100 mg/kg body weight. In subacute and chronic toxicity studies, clinical signs of intoxication are mainly behavioural disorders and convulsions, beginning at dose levels of 25 mg/kg. Clinical pathological alterations or morphological lesions, in particular neuropathological findings were not detected. Overall, the battery of mutagenicity studies shows no evidence of a genotoxic risk to man. Reproductive and developmental toxicity investigations and carcinogenicity studies were without substance-dependent findings. Toxicological and toxicokinetical data of both enantiomers did not show biologically relevant deviations in comparison to the data on tramadol. The toxicological characteristic of this compound is demonstrated.