Tramadol is a weak mu-opioid agonist with an additional mechanism that contributes to its efficacy in neuropathic pain. This additional mechanism is:

• A Inhibition of prostaglandin synthesis via COX-2 blockade
• B Blockade of NMDA glutamate receptors, reducing central sensitisation
• C Inhibition of neuronal reuptake of noradrenaline and serotonin (SNRI-like effect) ✓
• D Enhancement of GABA-A receptor-mediated inhibition in the spinal cord

Explanation

Tramadol has a dual mechanism: weak mu-opioid receptor agonism (approximately 6000-fold weaker than morphine for the parent compound) and inhibition of neuronal noradrenaline and serotonin reuptake (similar to SNRIs). The monoamine reuptake inhibition activates descending inhibitory pain pathways in the dorsal horn, contributing to its efficacy in neuropathic and chronic pain. This combined mechanism also explains its interactions with serotonergic drugs (risk of serotonin syndrome).

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

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Written and medically reviewed by the StethoPrep medical team.