title: Is tapentadol different from classical opioids? A review of the evidence.
abstract: Tapentadol is a single molecule able to deliver analgesia by two distinct mechanisms, a feature which differentiates it from many other analgesics. Pre-clinical data demonstrate two mechanisms of action: mu-opioid receptor agonist activity and noradrenaline re-uptake inhibition. From these, one may predict that tapentadol would be applicable across a broad spectrum of pain from nociceptive to neuropathic. The evidence in animal models suggests that norepinephrine re-uptake inhibition (NRI) is a key mechanism and may even predominate over opioid actions in chronic (and especially neuropathic) pain states, reinforcing that tapentadol is different to classical opioids and may, therefore, be an a priori choice for the treatment of neuropathic and mixed pain. The clinical studies and subsequent practice experience and surveillance support the concept of opioid and non-opioid mechanisms of action. The reduced incidence of some of the typical opioid-induced side effects, compared to equianalgesic doses of classical opioids, supports the hypothesis that tapentadol analgesia is only partially mediated by opioid agonist mechanisms. Both the pre-clinical and clinical profiles appear to be differentiated from those of classical opioids.
authors.affiliation: Barts Health NHS Trust, London, UK.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Langford
authors.affiliation: University of Nottingham, Nottingam, UK.
authors.forename: Roger
authors.initials: R
authors.lastname: Knaggs
authors.affiliation: Royal Marsden Hospital, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Farquhar-Smith
authors.affiliation: University College London, London, UK.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Dickenson
keywords: Tapentadol; analgesic mechanisms of action; analgesics; opioids; pain pharmacology