Tramadol achieves its main effect via an agonistic (activating) action at the so-called μ-opioid receptor. Tramadol also binds weakly to the other two known opioid receptors. In doing so, its affinity is 6000 times lower than that of morphine. By binding to these receptors, the perception of pain is dampened. However, tramadol has a second mechanism of action that is partly responsible for pain relief. Tramadol inhibits the reuptake of serotonin and norepinephrine into the presynapse, permanently increasing their concentration in the synaptic cleft. Both neurotransmitters are involved in pain transmission. As a result, pain is further additionally alleviated and mood is improved (antidepressant effect).
Tramadol is rapidly and almost completely absorbed via the gastrointestinal tract. The bioavailability is about 75%. The maximum plasma concentration of tramadol (after oral administration) is normally reached after 1-2 hours. Only 20% of the given dose is bound to plasma proteins. Tramadol is metabolized in the liver into at least 23 different metabolites. The enzyme that catalyzes these reactions is CYP2D6. 90% of the dose is ultimately excreted by the kidneys. the remaining 10% is excreted by the body in the stool. The elimination half-life is 5-6 hours.
Taking it together with bupropion or MAO inhibitors may cause serious side effects. In addition, concomitant use of centrally depressant substances, benzodiazepines, carbamazepine, anticoagulants and substances that increase serotonin levels (antidepressants, cocaine, ecstasy) should be avoided.