Tapentadol achieves analgesia through a dual mechanism. In addition to μ-opioid receptor agonism, it acts by:

• A Blocking NMDA receptors in the dorsal horn, reducing central sensitisation
• B Activating κ-opioid receptors in the periaqueductal grey matter
• C Inhibiting COX-3 isoenzyme in spinal dorsal horn neurons
• D Inhibiting serotonin and noradrenaline reuptake in spinal descending inhibitory pathways ✓

Explanation

Tapentadol is a centrally acting analgesic combining μ-opioid receptor agonism (primary for nociceptive pain) with noradrenaline reuptake inhibition in the spinal descending noradrenergic pathways (particularly effective for neuropathic pain). Unlike tramadol, it lacks significant serotonin reuptake inhibition and lacks serotonin-mediated side effects; its opioid component is stronger and it does not rely on metabolic conversion for efficacy.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.