Tapentadol shows lower intrinsic efficacy at µ receptor than morphine and oxycodone

Manandhar, Preeti; Connor, Mark; Santiago, Marina

doi:10.1002/prp2.921

Cited by 6 publications

(3 citation statements)

References 51 publications

(112 reference statements)

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“…Different preclinical and clinical studies pointed out the possibility to identify two distinct clusters of opioid drugs, based on their intrinsic efficacy and side effect profile (e.g., tolerability and abuse liability). On this basis, it is possible that buprenorphine and tapentadol, showing lower µ receptor intrinsic efficacy than morphine [ 49 , 50 ], might induce less oxidative stress and proteasome activation possibly associated with a more favorable side effect profile.…”

Section: Discussionmentioning

confidence: 99%

Effects of Different Opioid Drugs on Oxidative Status and Proteasome Activity in SH-SY5Y Cells

et al. 2022

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Opioids are the most effective drugs used for the management of moderate to severe pain; however, their chronic use is often associated with numerous adverse effects. Some results indicate the involvement of oxidative stress as well as of proteasome function in the development of some opioid-related side effects including analgesic tolerance, opioid-induced hyperalgesia (OIH) and dependence. Based on the evidence, this study investigated the impact of morphine, buprenorphine or tapentadol on intracellular reactive oxygen species levels (ROS), superoxide dismutase activity/gene expression, as well as β2 and β5 subunit proteasome activity/biosynthesis in SH-SY5Y cells. Results showed that tested opioids differently altered ROS production and SOD activity/biosynthesis. Indeed, the increase in ROS production and the reduction in SOD function elicited by morphine were not shared by the other opioids. Moreover, tested drugs produced distinct changes in β2(trypsin-like) and β5(chymotrypsin-like) proteasome activity and biosynthesis. In fact, while prolonged morphine exposure significantly increased the proteolytic activity of both subunits and β5 mRNA levels, buprenorphine and tapentadol either reduced or did not alter these parameters. These results, showing different actions of the selected opioid drugs on the investigated parameters, suggest that a low µ receptor intrinsic efficacy could be related to a smaller oxidative stress and proteasome activation and could be useful to shed more light on the role of the investigated cellular processes in the occurrence of these opioid drug side effects.

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Section: Discussionmentioning

confidence: 99%

Effects of Different Opioid Drugs on Oxidative Status and Proteasome Activity in SH-SY5Y Cells

et al. 2022

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“…Tapentadol has an onset of analgesic effect of 30 min and a half-life of 4 h. It reaches peak serum concentration within an hour after administration [ 52 ]. EC 50 was similar for both targets (1.8 μM for MOR, 2.3 μM for noradrenaline transporter) [ 55 ]. A total of 97% of the drug is metabolized by O -glucuronidation in the liver into inactive metabolites and subsequently excreted via the kidneys [ 52 ].…”

Section: Novel Opioidsmentioning

confidence: 99%

Novel Opioids in the Setting of Acute Postoperative Pain: A Narrative Review

Wang,

Murphy,

Shteynman

et al. 2023

Pharmaceuticals

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Although traditional opioids such as morphine and oxycodone are commonly used in the management of acute postoperative pain, novel opioids may play a role as alternatives that provide potent pain relief while minimizing adverse effects. In this review, we discuss the mechanisms of action, findings from preclinical studies and clinical trials, and potential advantages of several novel opioids. The more established include oliceridine (biased ligand activity to activate analgesia and downregulate opioid-related adverse events), tapentadol (mu-opioid agonist and norepinephrine reuptake inhibitor), and cebranopadol (mu-opioid agonist with nociceptin opioid peptide activity)—all of which have demonstrated success in the clinical setting when compared to traditional opioids. On the other hand, dinalbuphine sebacate (DNS; semi-synthetic mu partial antagonist and kappa agonist), dual enkephalinase inhibitors (STR-324, PL37, and PL265), and endomorphin-1 analog (CYT-1010) have shown good efficacy in preclinical studies with future plans for clinical trials. Rather than relying solely on mu-opioid receptor agonism to relieve pain and risk opioid-related adverse events (ORAEs), novel opioids make use of alternative mechanisms of action to treat pain while maintaining a safer side-effect profile, such as lower incidence of nausea, vomiting, sedation, and respiratory depression as well as reduced abuse potential.

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“…As none of Tapentadol’s metabolites are analgesic, and it is metabolized by hepatic glucuronidation, not cytochrome P450 enzymes, it has fewer drug–drug interactions and interindividual variability due to cytochrome P450 genetic polymorphisms compared to tramadol and other opioids; clearance is reduced by hepatic dysfunction 1▪▪,11,13. As a low-efficacy MOR agonist 14▪, with up to a 50 times lower MOR binding affinity compared to morphine 6▪▪, tapentadol has the potential for fewer opioid adverse effects 5. In preclinical pain models, it provides highly effective analgesia comparable to morphine and oxycodone, despite moderate MOR affinity and relatively moderate NRI activity 6▪▪,10.…”

Section: Introductionmentioning

confidence: 99%

Tapentadol for the management of cancer pain in adults: an update

Boland¹

2023

Current Opinion in Supportive &Amp; Palliative Care

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Purpose of reviewTapentadol is the first of a new class of analgesics, having synergistic µ-opioid receptor agonist and noradrenaline reuptake inhibitory actions. It has been widely researched in many areas of pain, often in noninferiority studies against potent opioids. This review describes all randomized and recent nonrandomized studies of tapentadol in adults with cancer pain. Recent findingsTapentadol has been shown to be at least as effective as morphine and oxycodone in five randomized (two of which were multicenter and double-blind) and a range of nonrandomized trials, although caution is needed when interpreting these results. It is effective in both opioid-naive patients and those already taking opioids. By having a lower µ-opioid receptor binding affinity, it has fewer opioid-related toxicities such as constipation and nausea. A recent randomized trial comparing tapentadol to tapentadol plus duloxetine in patients with chemotherapy-induced peripheral neuropathy shows similar improvement in both groups in a range of pain relieving and quality of life measures, with similar adverse effects.

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Tapentadol shows lower intrinsic efficacy at µ receptor than morphine and oxycodone

Cited by 6 publications

References 51 publications

Effects of Different Opioid Drugs on Oxidative Status and Proteasome Activity in SH-SY5Y Cells

Effects of Different Opioid Drugs on Oxidative Status and Proteasome Activity in SH-SY5Y Cells

Novel Opioids in the Setting of Acute Postoperative Pain: A Narrative Review

Tapentadol for the management of cancer pain in adults: an update

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