Mechanistic and functional differentiation of tapentadol and tramadol

  title={Mechanistic and functional differentiation of tapentadol and tramadol},
  author={Robert B Raffa and Helmut Heinrich Buschmann and Thomas Christoph and Gary M. Eichenbaum and Werner Englberger and Christopher M. Flores and Torsten Hertrampf and Babette Y. K{\"o}gel and Klaus Schiene and Wolfgang Werner A Strassburger and Rolf Dr Terlinden and Thomas M Tzschentke},
  journal={Expert Opinion on Pharmacotherapy},
  pages={1437 - 1449}
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… 
Comparative pharmacology and toxicology of tramadol and tapentadol
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Comparative metabolism of tramadol and tapentadol: a toxicological perspective
A thorough knowledge about tramadol and tapentadol metabolomics is expected to provide additional insights to better understand the interindividual variability in their pharmacokinetics and dose-responsiveness, and contribute to the establishment of personalized therapeutic approaches, minimizing side effects and optimizing analgesic efficacy.
Tapentadol Versus Tramadol: A Narrative and Comparative Review of Their Pharmacological, Efficacy and Safety Profiles in Adult Patients
Tapentadol is not a first-line opioid but represents an additional analgesic in the therapeutic choices, which some patients may benefit from after careful examination of their clinical situation, co-morbidities and co-medications.
Is tapentadol different from classical opioids? A review of the evidence
The clinical studies and subsequent practice experience and surveillance support the concept of opioid and non-opioid mechanisms of action, and the reduced incidence of some of the typical opioid-induced side effects, supports the hypothesis that tapentadol analgesia is only partially mediated by opioid agonist mechanisms.
Tapentadol: an analgesic that differs from classic opioids due to its noradrenergic mechanism of action.
Tapentadol represents a great innovation in chronic pain therapy with a unique analgesic profile different form classical opioids, therefore, thanks to its synergistic MOR-NRI action, it may be a good option for the treatment of chronic, neuropathic and mixed pain.
The switch from buprenorphine to tapentadol: is it worth?
  • A. Miclescu
  • Medicine, Biology
    Romanian journal of anaesthesia and intensive care
  • 2016
The evidence to support the method used for transdermal buprenorphine rotation to tapentadol is weak and both drugs show particular pharmacodynamic and pharmacokinetic properties which reduce the risks of development of tolerance, opioid abuse, diversion and determine fewer hormone changes than the "classical opioids" making these opioids more attractive than other opioids in long term opioid treatment.
The Mu-Opioid Receptor Agonist/Noradrenaline Reuptake Inhibition (MOR–NRI) Concept in Analgesia: The Case of Tapentadol
It is suggested that tapentadol is the first representative of a proposed new class of analgesics, MOR–NRI, such that relatively moderate activity at the two target sites (MOR and noradrenaline reuptake transporter) is sufficient to produce strong analgesic effects.
Does ‘Strong Analgesic’ Equal ‘Strong Opioid’? Tapentadol and the Concept of ‘µ-Load’
This work applied standard drug–receptor theory and novel techniques to in vitro and in vivo data to estimate the μ-load of tapentadol (the % contribution of the opioid component to the adverse effect magnitude relative to a pure/classical µ-opioid at equianalgesia) in respiratory depression and constipation, and compared the results to clinical evidence.


In vitro and in vivo characterization of tapentadol metabolites.
It is highly unlikely that tapentadol forms metabolites that contribute in any relevant degree to its analgesic activity, as most of these metabolites had no analgesic effects in the tail-flick test in mice.
Tramadol--the impact of its pharmacokinetic and pharmacodynamic properties on the clinical management of pain.
  • U. Klotz
  • Medicine, Biology
  • 2003
Tramadol is an effective and safe analgesic with a very low interaction potential and represents a drug of first choice if moderate to severe pain states have to be treated in pediatric, adult and elderly patients including those with poor cardiopulmonary function.
[Pharmacology of tramadol].
Tramadol is a central acting analgesic which has been shown to be effective and well tolerated, and likely to be of value for treating several pain conditions where treatment with strong opioids is not required.
Synergistic Interaction between the Two Mechanisms of Action of Tapentadol in Analgesia
A very pronounced synergistic interaction between the two mechanisms of action of tapentadol is demonstrated, probably the first demonstration of a synergistic interactions between the occupied receptors for a single compound with two mechanism of action.
Role of active metabolites in the use of opioids
Clinicians need to be aware that many opioids have active metabolites that will become therapeutically important, for example in cases of altered pathology, drug interactions and genetic polymorphisms of drug-metabolizing enzymes.
Extended-release Tramadol (ULTRAM ER): a pharmacotherapeutic, pharmacokinetic, and pharmacodynamic focus on effectiveness and safety in patients with chronic/persistent pain.
  • R. Barkin
  • Medicine
    American journal of therapeutics
  • 2008
Tramadol ER has been shown to be safe and well-tolerated and may be a suitable alternative for patients with inadequate analgesic response or contraindications to use of nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors.
Complementary and synergistic antinociceptive interaction between the enantiomers of tramadol.
A rational explanation for the coexistence of dual components to tramadol-induced antinociception appears to be related to the different, but complementary and interactive, pharmacologies of its enantiomers and might form the basis for understanding its clinical profile.
Analgesics : from chemistry and pharmacology to clinical application
This chapter discusses the development of new approaches in pain management using Gabapentin, as well as existing approaches, and investigates their applications in the context of pain management today.