ArticleThe Journal of pharmacology and experimental therapeutics2011
Synergistic interaction between the two mechanisms of action of tapentadol in analgesia.
Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development.International journal of molecular sciences · 2022Pooled it
- A Multicenter, Randomized, Open-Label, Active-Controlled, Parallel-Group Study Evaluating the Pharmacokinetics of Single-Dose Tapentadol Hydrochloride Intravenous Infusion and Tapentadol Hydrochloride Oral Tablets in Patients with Pain.European journal of drug metabolism and pharmacokinetics · 2025Trial
- A Randomized Controlled Trial on the Effect of Tapentadol and Morphine on Conditioned Pain Modulation in Healthy Volunteers.PloS one · 2015Trial
- Mixed-mechanism analgesics for mixed pain.Frontiers in medicine · 2025Article
- Tapentadol shows lower intrinsic efficacy at µ receptor than morphine and oxycodone.Pharmacology research & perspectives · 2022Article
- Exploiting Injury-Induced Peripheral Opioid Receptor Changes in Novel Analgesic Development for Chronic Pain.Frontiers in pain research (Lausanne, Switzerland) · 2022Article
- Shedding Light on the Pharmacological Interactions between μ-Opioid Analgesics and Angiotensin Receptor Modulators: A New Option for Treating Chronic Pain.Molecules (Basel, Switzerland) · 2021Review
- Cost-Effectiveness Analysis of Tapentadol Versus Oxycodone/Naloxone in both Branded and Generic Formulations in Patients with Musculoskeletal Pain.Clinical drug investigation · 2021Article
- Effectiveness of tapentadol hydrochloride for treatment of orthopedic pain in dogs: A pilot study.The Canadian veterinary journal = La revue veterinaire canadienne · 2020Article
- Population Pharmacokinetics of Tapentadol in Children from Birth to <18 Years Old.Journal of pain research · 2020Article
- Tapentadol vs oxycodone/naloxone in the management of pain after total hip arthroplasty in the fast track setting: an observational study.Journal of experimental orthopaedics · 2019Article
- A combination pharmacotherapy of tapentadol and pregabalin to tackle centrally driven osteoarthritis pain.European journal of pain (London, England) · 2019Article
- Monoamines as Drug Targets in Chronic Pain: Focusing on Neuropathic Pain.Frontiers in neuroscience · 2019Review
- Pharmacological rationale for tapentadol therapy: a review of new evidence.Journal of pain research · 2019Review
- Synergistic interaction between the agonism of cebranopadol at nociceptin/orphanin FQ and classical opioid receptors in the rat spinal nerve ligation model.Pharmacology research & perspectives · 2018Article
- Review
- Does 'Strong Analgesic' Equal 'Strong Opioid'? Tapentadol and the Concept of 'µ-Load'.Advances in therapy · 2018Article
- Tapentadol Extended Release in the Treatment of Severe Chronic Low Back Pain and Osteoarthritis Pain.Pain and therapy · 2018Review
- Opioid-induced inhibition of the human 5-HT and noradrenaline transporters in vitro: link to clinical reports of serotonin syndrome.British journal of pharmacology · 2018Article
- Review of Post-Marketing Safety Data on Tapentadol, a Centrally Acting Analgesic.Advances in therapy · 2018Review
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
7 authors.
Funding
Abstract
The novel centrally acting analgesic tapentadol [(-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride] combines two mechanisms of action, μ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition (NRI), in a single molecule. Pharmacological antagonism studies have demonstrated that both mechanisms of action contribute to the analgesic effects of tapentadol. This study was designed to investigate the nature of the interaction of the two mechanisms. Dose-response curves were generated in rats for tapentadol alone or in combination with the opioid antagonist naloxone or the α(2)-adrenoceptor antagonist yohimbine. Two different pain models were used: 1) low-intensity tail-flick and 2) spinal nerve ligation. In each model, we obtained dose-effect relations to reveal the effect of tapentadol based on MOR agonism, NRI, and unblocked tapentadol. Receptor fractional occupation was determined from tapentadol's brain concentration and its dissociation constant for each binding site. Tapentadol produced dose-dependent analgesic effects in both pain models, and its dose-effect curves were shifted to the right by both antagonists, thereby providing data to distinguish between MOR agonism and NRI. Both isobolographic analysis of occupation-effect data and a theoretically equivalent methodology determining interactions from the effect scale demonstrated very pronounced synergistic interaction between the two mechanisms of action of tapentadol. This may explain why tapentadol is only 2- to 3-fold less potent than morphine across a variety of preclinical pain models despite its 50-fold lower affinity for the MOR. This is probably the first demonstration of a synergistic interaction between the occupied receptors for a single compound with two mechanisms of action.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.