The experimental toxicology of tramadol: an overview

Toxicol Lett. 1998 Mar 16;95(1):63-71. doi: 10.1016/s0378-4274(98)00023-x.


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.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / toxicity*
  • Animals
  • Behavior, Animal / drug effects
  • Carcinogenicity Tests
  • Dose-Response Relationship, Drug
  • Humans
  • Lethal Dose 50
  • Male
  • Mutagenicity Tests
  • Reproduction / drug effects
  • Stereoisomerism
  • Tramadol / administration & dosage
  • Tramadol / pharmacokinetics
  • Tramadol / toxicity*


  • Analgesics, Opioid
  • Tramadol