Mechanistic and functional differentiation of tapentadol and tramadol

Expert Opin Pharmacother. 2012 Jul;13(10):1437-49. doi: 10.1517/14656566.2012.696097. Epub 2012 Jun 15.

Abstract

Introduction: Many opioid analgesics share common structural elements; however, minor differences in structure can result in major differences in pharmacological activity, pharmacokinetic profile, and clinical efficacy and tolerability.

Areas covered: This review compares and contrasts the chemistry, pharmacodynamics, pharmacokinetics, and CNS 'functional activity' of tapentadol and tramadol, responsible for their individual clinical utilities.

Expert opinion: The distinct properties of tapentadol and tramadol generate different CNS functional activities, making each drug the prototype of different classes of opioid/nonopioid analgesics. Tramadol's analgesia derives from relatively weak µ-opioid receptor (MOR) agonism, plus norepinephrine and serotonin reuptake inhibition, provided collectively by the enantiomers of the parent drug and a metabolite that is a stronger MOR agonist, but has lower CNS penetration. Tapentadol's MOR agonist activity is several-fold greater than tramadol's, with prominent norepinephrine reuptake inhibition and minimal serotonin effect. Accordingly, tramadol is well-suited for pain conditions for which a strong opioid component is not needed-and it has the benefit of a low abuse potential; whereas tapentadol, a schedule-II controlled substance, is well-suited for pain conditions requiring a strong opioid component-and it has the benefit of greater gastrointestinal tolerability compared to classical strong opioids. Both drugs offer distinct and complementary clinical options.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / chemistry
  • Analgesics, Opioid / pharmacology*
  • Analgesics, Opioid / therapeutic use
  • Animals
  • Humans
  • Pain / drug therapy
  • Phenols / chemistry
  • Phenols / pharmacology*
  • Phenols / therapeutic use
  • Receptors, Opioid, mu / agonists
  • Tapentadol
  • Tramadol / chemistry
  • Tramadol / pharmacology*
  • Tramadol / therapeutic use

Substances

  • Analgesics, Opioid
  • Phenols
  • Receptors, Opioid, mu
  • Tramadol
  • Tapentadol