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Tramadol: Mechanism of Action

Tramadol is a centrally acting synthetic opioid medication with monoaminergic actions similar to serotonin norepinephrine reuptake inhibitors (SNRIs). It specifically acts as a weak mu-opioid receptor agonist and as a serotonin and norepinephrine reuptake inhibitor. Genetic polymorphisms modulating CYP enzyme activities (CVP2D6 >> CYP3A4) are the main source of variability in patients’ analgesic response. Perioperative considerations include decreased seizure threshold and increased risk of serotonin syndrome with coadministration of proserotonergic medications (i.e. SSRIs, SNRIs, TCAs, MAOIs, triptans, antipsychotics, anticonvulsants, antiparkinsonian agents, dextromethorphan, St John’s wort, etc.).


  1. Miotto K, et al. Trends in Tramadol: Pharmacology, Metabolism, and Misuse. Anesth Analg. 2017 Jan;124(1):44-51. PubMed Link