Tapentadol (trade name Nucynta, Palexia, In India - ZYNTAP) is a centrally acting analgesic with a dual mode of action as an agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor. It is also an agonist of the σ₂ receptor, though the function of this orphan receptor remains controversial. While its analgesic actions have been compared to tramadol and oxycodone, its general potency is somewhere between tramadol and morphine in effectiveness. It has opioid and nonopioid acitivity in a single compound.

In the US, Tapentadol is FDA approved for the treatment of moderate to severe acute pain. Due to the dual mechanism of action as an opioid agonist and norepinephrine reuptake inhibitor, there is potential for off label use in chronic pain.

Doctors use serotonin and norepinephrine reuptake inhibitors in chronic pain management to increase the effectiveness of opioids and, to a lesser extent, NSAIDs (along with other analgesics) against neuropathic pain and from certain specific contributing causes such as fibromyalgia and diabetic neuropathy. One selective serotonin and norepinephrine reuptake inhibitor (SNRI) often used as an adjunct, atypical & potentiator is duloxetine (Cymbalta). Another opioid with selective norepinephrine reuptake inhibitor effects is levorphanol (Levo-Dromoran).