Tramadol's analgesic action is mediated by two distinct mechanisms. Which of the following correctly identifies both?

• A Weak mu-opioid receptor agonism, AND inhibition of serotonin and norepinephrine reuptake ✓
• B Kappa-opioid receptor agonism AND NMDA receptor antagonism
• C Delta-opioid receptor agonism AND COX-2 inhibition
• D Full mu-opioid agonism AND GABA-A potentiation

Explanation

Tramadol exerts analgesia via two complementary mechanisms: (1) weak mu-opioid receptor agonism (1/6000 the potency of morphine at mu receptors), mainly through its active metabolite O-desmethyltramadol (M1), which has 200-fold higher mu affinity than tramadol itself; and (2) central monoaminergic reuptake inhibition (serotonin and norepinephrine), activating descending inhibitory pain pathways. Because of the SNRI component, tramadol lowers the seizure threshold and can precipitate serotonin syndrome when combined with other serotonergic agents. It is NOT a COX inhibitor, NMDA antagonist, or GABA potentiator.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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