Tramadol Dual Mechanism — MFDS Part 1 MCQ
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Correct answer: D — Inhibition of neuronal noradrenaline reuptake with enhancement of serotonin release
Option D is correct. Tramadol is a centrally acting analgesic with opioid-receptor agonist activity, greatest at the mu receptor. Its additional monoaminergic analgesic actions are inhibition of neuronal noradrenaline reuptake and enhancement of serotonin release. This serotonergic activity helps explain the risk of serotonin syndrome when tramadol is combined with serotonergic medicines. GABA-A receptor modulation is characteristic of drugs such as benzodiazepines, while COX-2 inhibition is an NSAID mechanism. Dopamine D2 antagonism is associated mainly with antipsychotic and antiemetic activity. NMDA receptor antagonism contributes to the actions of agents such as ketamine, but is not the additional mechanism specified for tramadol in the UK SmPC.
Reference: Brown & Burk UK Ltd. Tramadol hydrochloride 50 mg capsules, hard: Summary of Product Characteristics, section 5.1 Pharmacodynamic properties. Updated 9 July 2026. https://www.medicines.org.uk/emc/product/11799/smpc