Tramadol produces analgesia through a dual mechanism. In addition to weak mu-opioid receptor agonism, it also inhibits reuptake of which neurotransmitters to contribute to its analgesic effect?

• A Dopamine and GABA
• B Glutamate and substance P
• C Acetylcholine and histamine
• D Noradrenaline and serotonin ✓

Explanation

Tramadol's analgesia is mediated by two complementary mechanisms: (1) the O-desmethyltramadol (M1) metabolite is a weak mu-opioid agonist, and (2) the parent compound inhibits neuronal reuptake of noradrenaline (enhancing descending inhibitory noradrenergic pathways) and serotonin (enhancing descending serotonergic inhibition). Because of the serotonin reuptake inhibition component, tramadol carries a risk of serotonin syndrome when combined with SSRIs, MAOIs or other serotonergic drugs — a clinically important drug interaction.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.