Tramadol produces analgesia by two distinct mechanisms. Which combination correctly describes both?

• A Selective μ-opioid agonism and inhibition of prostaglandin synthesis via COX inhibition
• B Weak μ-opioid receptor agonism and inhibition of neuronal norepinephrine and serotonin reuptake ✓
• C κ-Opioid receptor agonism and NMDA receptor antagonism
• D δ-Opioid agonism and GABA-A receptor potentiation

Explanation

Tramadol has two complementary analgesic mechanisms: (1) weak μ-opioid receptor agonism (approximately 10-fold weaker than morphine), and (2) inhibition of neuronal reuptake of both norepinephrine and serotonin (monoaminergic mechanism), enhancing descending pain modulation. The monoaminergic component explains why tramadol's analgesia is only partially reversed by naloxone. This dual mechanism also underlies its risk of serotonin syndrome when combined with SSRIs or MAO inhibitors. It does not significantly inhibit COX, antagonise NMDA, or potentiate GABA-A receptors.

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

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