Tapentadol is a synthetic analgesic opioid with dual mechanism of action as a mu opioid agonist, and a norepinephrine reuptake inhibtor. It is an agonist of mu, kappa, and delta opioid receptors. It is also a weak serotonin reuptake inhibitor, but that doesn't contribute to the analgesic effect. Tapentadol binds to mu opioid receptors on the presynaptic membrane, stimulating the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as GABA is inhibited. Opioids close N-type voltage-operated calcium channels and open calcium-dependent inwardly rectifying potassium channels. This results in hyperpolarization and reduced neuronal excitability. Morphine acts at A delta and C pain fibres in the dorsal horn of the spinal cord. By decreasing neurotransmitter action there is less pain transmittance into the spinal cord. This leads to less pain perception.

Tapentadol Opioid Agonist Pathway References