THE EXPERIMENTAL TOXICOLOGY OF TRAMADOL - AN OVERVIEW

The experimental toxicological findings of tramadol are reviewed and d iscussed. Tramadol is a centrally acting analgesic. In acute toxicity studies, LD50 values are estimated to be around 300-350 mg/kg body wei ght (rat, mouse, oral administration). After intravenous administratio n the LD50 values ranged from 50 to 100 mg/kg body weight. In subacute and chronic toxicity studies, clinical signs of intoxication are main ly 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, t he battery of mutagenicity studies shows no evidence of a genotoxic ri sk to man. Reproductive and developmental toxicity investigations and carcinogenicity studies were without substance-dependent findings. Tox icological and toxicokinetical data of both enantiomers did not show b iologically relevant deviations in comparison to the data on tramadol. The toxicological characteristic of this compound is demonstrated. (C ) 1998 Elsevier Science Ireland Ltd. All rights reserved.