Question: Tramadol has been marketed in the United States for more than 29 years to treat mild-to-moderate pain. What are the two mechanisms by which this drug produces analgesia?
Answer: The cited reference notes that tramadol “…..has minimal affinity for the mu-opioid receptor and inhibits the reuptake of serotonin and norepinephrine. The active hepatic metabolite, o-desmethyltramadol or M1, is an opioid agonist with high relative intrinsic efficacy and moderate affinity for the mu-opioid receptor.” (Babalonis S et al. Abuse liability and reinforcing efficacy of oral tramadol in humans. 2013 Drug Alc Dep 129:116-124)