Tramadol's analgesic mechanism differs from pure opioids. In addition to weak mu opioid receptor agonism, it acts by:

• A Inhibiting COX-1 and COX-2 like NSAIDs
• B Activating GABA-B receptors in the spinal cord
• C Inhibiting reuptake of both serotonin and noradrenaline, activating descending inhibitory pain pathways ✓
• D Blocking NMDA glutamate receptors in the dorsal horn

Explanation

Tramadol is a dual-mechanism analgesic: it is a weak mu opioid agonist and also inhibits the reuptake of serotonin and noradrenaline in spinal and supraspinal descending inhibitory pathways. This monoamine reuptake inhibition provides additional analgesia beyond its opioid effect and contributes to its risk of serotonin syndrome when combined with other serotonergic drugs. Because it is a weak opioid, it carries less respiratory depression risk but can still cause dependence.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.