DOCSLIB.ORG

R22. Oliceridine's Role in Pain Management: a Qualitative Literature

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
R22. Oliceridine's Role in Pain Management: a Qualitative Literature University of Mississippi eGrove Annual Poster Session Pharmacy, School of 10-23-2020 R22. Oliceridine’s role in pain management: a qualitative literature review Hallie Austin University of Mississippi, [email protected] Melissa Reilly University of Mississippi Follow this and additional works at: https://egrove.olemiss.edu/pharm_annual_posters Recommended Citation Austin, Hallie and Reilly, Melissa, "R22. Oliceridine’s role in pain management: a qualitative literature review" (2020). Annual Poster Session. 22. https://egrove.olemiss.edu/pharm_annual_posters/22 This Book is brought to you for free and open access by the Pharmacy, School of at eGrove. It has been accepted for inclusion in Annual Poster Session by an authorized administrator of eGrove. For more information, please contact [email protected]. OLICERIDINE’S ROLE IN PAIN MANAGEMENT: A QUALITATIVE LITERATURE REVIEW Melissa Reilly, PharmD, BCGP, Hallie Austin, PharmD candidate 2023 INTRODUCTION • Oliceridine (Olinvyk) is a novel opioid for moderate to severe pain management for use in the clinical setting. • As an opioid agonist, it is relatively selective for the mu- opioid receptor, and it serves as the first mu-opioid receptor G protein pathway selective modulator. • With its novel mechanism of action, oliceridine was designed to improve μ-opioid receptor pharmacology and decrease opioid related adverse effects. OBJECTIVES This literature review sought to identify the role oliceridine may have in pain management in clinical practice. • Study design • Qualitative literature review METHODS • 2014-2019 • Search terms • PubMed - “oliceridine” METHODS INCLUSION CRITERIA EXCLUSION CRITERIA Randomized control trial Review articles Open label Pharmacokinetic & pharmacodynamic modeling trials RESULTS: RESULTS 41studies populated from “oliceridine” search 6 studies included 35 studies excluded Reason for exclusion: Animal PK/PD Review study study articles 10 8 17 Study Baseline Intervention Controls Results Characteristics Singla, et al.1 No. 401 (loading dose, Placebo Respiratory Safety Burden: O vs. placebo (efficacy) Age 18 – 75 demand dose) Oliceridine vs placebo: P > 0.05 O 0.1 mg: P = 0.029 2019 O: Morphine vs. placebo: P < 0.05 O 0.35 mg: P < 0.0001 1.5 mg, 0.1 mg O 0.5 mg: P = 0.0004 1.5 mg, 0.35 mg GI adverse effects: 1.5 mg, 0.5 mg O: 0.1 mg: 49.4%; 0.35 mg: 65.8%; M (1 mg) vs. placebo 0.5 mg: 78.8% 78.3% (P < 0.001) M: placebo: 47.0% 4 mg, 1 mg M: 79.3% Bergese, et No. 768 O: placebo The incidence of AEs leading to rapid reduction in NRS pain score by 2.2 ± 2.3 at al.2 Age 18 - 89 0.9 to 223.5 mg early discontinuation and serious 30 mins from a score of 6.3 ± 2.1 (at baseline) 2019 AEs were 2% and 3%, respectively. which was maintained to the end of treatment. Viscusi, et No. 389 (loading dose, placebo Respiratory Safety Burden: O vs. placebo: all P<0.0001 al.3 Age 18 - 75 demand dose) -supplemental oxygen: 2019 O: O vs M % treatment responders: 1.5 mg, 0.1 mg P<0.01 Placebo: 15.2% 1.5 mg, 0.35 mg O 0.1 mg: 50% 1.5 mg, 0.5 mg GI adverse effects: O 0.35 mg: 62% O vs M O 0.5 mg: 65.8% M: P<0.05 M 1 mg: 71.1% 4 mg, 1 mg O: oliceridine M: morphine Study Baseline Intervention Controls Results Characteristics Singla, et al.4 No. 200 (loading dose, demand dose) Placebo O 0.1 mg vs placebo: P=0.0001 2017 (Oct) Age 18-65 O: O 0.35 mg vs placebo: P=0.0005 A: 1.5 mg, 0.1 mg (n=39) B: 1.5 mg, 0.35 mg (n=39) M vs placebo: P<0.0001 M: O 0.1 and 0.35 mg vs M 1 mg: 4 mg, 1 mg (n=83) Nausea: P<0.01 Vomiting: P<0.01 Respiratory effects: P<0.05 Viscusi, et al. 5 No. 400 O: 0.5, 1, 2, & 3 mg Placebo O v Placebo 2016 Age 18-75 O 0.5 mg; P = 0.1832 M: 4 mg O 1 mg; P = 0.2311 O 2 mg; P = 0.0024 O 3mg; P < 0.0001 M 4 mg vs. Placebo: P = 0.0023 Soergel, et al. 6 No. 30 O: Placebo O vs placebo: 2014 Age 18-50 1.5, 3, 4.5 mg O 3 & 4.5mg (P < .02) 1.5-mg (P < .007) O v M: 3 mg (P < .02;) 4.5 mg (P < .005) O: oliceridine M: morphine RESULTS: EFFICACY Oliceridine vs. placebo: Oliceridine vs morphine: -Most studies reviewed had significant -Most studies reviewed did not have P values, providing evidence for efficacy significant P values, providing evidence for 1,2,3,4,6 against placebo. less efficacy against morphine.6 -Measurements looked at for efficacy -Only one study conducted by Soergel and include responder rates1,3, pain scores2,4, NRS TWA0-48, changes5, and colleagues had significant findings for CPT hand removal latencies.6 oliceridine’s efficacy compared to morphine’s efficacy.1,2,3,4,5 -Only one study conducted by Viscusi and colleagues showed no significance -Although the 3 and 4.5 mg oliceridine in oliceridine’s (low dose) efficacy doses were both proven efficacious against compared to the placebo. morphine, the higher dose was more significant. (O 3 mg: P < .02; O 4.5 mg: P < .005)6 Oliceridine vs morphine: • Most studies showed a tolerable safety profile in regard to adverse effects. • A study conducted by N Singla, HS Minkowitz, and colleagues demonstrated that oliceridine has an acceptable safety/tolerability profile and potentially wider therapeutic window than morphine. • ER Viscusi and colleagues also demonstrated RESULTS: favorable safety and tolerability regarding GI SAFETY and respiratory effects compared to morphine.3 • the supplemental oxygen requirements for the oliceridine 0.1, 0.35, and 0.5 mg groups were significantly less than the morphine 1 mg group (p < 0.01). • GI adverse effects for the oliceridine 0.1, 0.35, and 0.5 mg groups were significantly less than the morphine 1 mg group (p < 0.05). • Several other studies reviewed showed similar results. • Comparisons: • None of the studies reviewed compared oliceridine to non-opioids. • The only other opioid that oliceridine has been compared to from our pool of studies is morphine. • Dosing • Equianalgesic dosing has not yet been defined so RESULTS: comparative doses of oliceridine and morphine LIMITATIONS was inconsistent. • In a study conducted by SD Bergese and colleagues, no control group or comparator group was used. • Most studies looked at efficacy of oliceridine compared to placebo only rather than also looking at oliceridine vs morphine efficacy. CONCLUSION • Based on currently available literature, oliceridine’s use in clinical practice is limited to patient populations undergoing procedures such as abdominoplasties & bunioectomies or that have painful non-surgical medical conditions. • In addition, most studies conducted have looked only at oliceridine efficacy and safety regarding side effects, but none have looked at reducing abuse potential in humans. • One study by C Zamarripa, SR Edwards, and colleagues demonstrates that TRV130 produces reinforcing and antinociceptive effects that are quantitatively similar to oxycodone, and that a biased-signaling profile does not necessarily reduce abuse potential. 7 • Even though this study was conducted in rats, it could be argued that this effect could be similar in humans. • Do we really need a new IV opioid during an opioid epidemic when we should focus more of our resources on finding more novel non-opioid interventions and therapies? Future studies should evaluate oliceridine compared to other APPLICATIONS available intravenous opioids and TO CLINICAL PRACTICE non-opioids as far as efficacy, safety, dependency, and costs. • 1. Singla NK, Skobieranda F, Soergel DG, et al. APOLLO-2: A Randomized, Placebo and Active-Controlled Phase III Study Investigating Oliceridine (TRV130), a G Protein-Biased Ligand at the μ-Opioid Receptor, for Management of Moderate to Severe Acute Pain Following Abdominoplasty. Pain Pract. 2019;19(7):715- 731. doi:10.1111/papr.12801 • 2. Bergese SD, Brzezinski M, Hammer GB, et al. ATHENA: A Phase 3, Open-Label Study Of The Safety And Effectiveness Of Oliceridine (TRV130), A G-Protein Selective Agonist At The µ- Opioid Receptor, In Patients With Moderate To Severe Acute Pain REFERENCES Requiring Parenteral Opioid Therapy. J Pain Res. 2019;12:3113- 3126. Published 2019 Nov 14. doi:10.2147/JPR.S217563 • 3. Viscusi ER, Skobieranda F, Soergel DG, Cook E, Burt DA, Singla N. APOLLO-1: a randomized placebo and active-controlled phase III study investigating oliceridine (TRV130), a G protein-biased ligand at the µ-opioid receptor, for management of moderate-to- severe acute pain following bunionectomy. J Pain Res. 2019 Mar 11;12:927-943. doi: 10.2147/JPR.S171013. PMID: 30881102; PMCID: PMC6417853. • 4. Singla N, Minkowitz HS, Soergel DG, Burt DA, Subach RA, Salamea MY, Fossler MJ, Skobieranda F. A randomized, Phase IIb study investigating oliceridine (TRV130), a novel µ- receptor G-protein pathway selective (μ-GPS) modulator, for the management of moderate to severe acute pain following abdominoplasty. J Pain Res. 2017 Oct 6;10:2413-2424. doi: 10.2147/JPR.S137952. PMID: 29062240; PMCID: PMC5638571. • 5. Viscusi ER, Webster L, Kuss M, et al. A randomized, phase 2 study investigating TRV130, a biased ligand of the μ-opioid receptor, for the intravenous treatment of acute pain. Pain. REFERENCES 2016;157(1):264-272. doi:10.1097/j.pain.0000000000000363 • 6. Soergel DG, Subach RA, Burnham N, et al. Biased agonism CONTINUED of the μ-opioid receptor by TRV130 increases analgesia and reduces on-target adverse effects versus morphine: A randomized, double-blind, placebo-controlled, crossover study in healthy volunteers.
Load more

Recommended publications
  • Ong Edmund W 201703 Phd.Pdf (5.844Mb)
    INVESTIGATING THE EFFECTS OF PROLONGED MU OPIOID RECEPTOR ACTIVATION UPON OPIOID RECEPTOR HETEROMERIZATION by Edmund Wing Ong A thesis submitted to the Graduate Program in Pharmacology & Toxicology in the Department of Biomedical and Molecular Sciences In conformity with the requirements for the degree of Doctor of Philosophy Queen’s University Kingston, Ontario, Canada March, 2017 Copyright © Edmund Wing Ong, 2017 Abstract Opioid receptors are the sites of action for morphine and most other clinically-used opioid drugs. Abundant evidence now demonstrates that different opioid receptor types can physically associate to form heteromers. Owing to their constituent monomers’ involvement in analgesia, mu/delta opioid receptor (M/DOR) heteromers have been a particular focus of attention. Understandings of the physiological relevance of M/DOR formation remain limited in large part due to the reliance of existing M/DOR findings upon contrived heterologous systems. This thesis investigated the physiological relevance of M/DOR generation following prolonged MOR activation. To address M/DOR in endogenous tissues, suitable model systems and experimental tools were established. This included a viable dorsal root ganglion (DRG) neuron primary culture model, antisera specifically directed against M/DOR, a quantitative immunofluorescence colocalizational analysis method, and a floxed-Stop, FLAG-tagged DOR conditional knock-in mouse model. The development and implementation of such techniques make it possible to conduct experiments addressing the nature of M/DOR heteromers in systems with compelling physiological relevance. Seeking to both reinforce and extend existing findings from heterologous systems, it was first necessary to demonstrate the existence of M/DOR heteromers. Using antibodies directed against M/DOR itself as well as constituent monomers, M/DOR heteromers were identified in endogenous tissues and demonstrated to increase in abundance following prolonged mu opioid receptor (MOR) activation by morphine.
    [Show full text]
  • Biased Versus Partial Agonism in the Search for Safer Opioid Analgesics
    molecules Review Biased versus Partial Agonism in the Search for Safer Opioid Analgesics Joaquim Azevedo Neto 1 , Anna Costanzini 2 , Roberto De Giorgio 2 , David G. Lambert 3 , Chiara Ruzza 1,4,* and Girolamo Calò 1 1 Department of Biomedical and Specialty Surgical Sciences, Section of Pharmacology, University of Ferrara, 44121 Ferrara, Italy; [email protected] (J.A.N.); [email protected] (G.C.) 2 Department of Morphology, Surgery, Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy; [email protected] (A.C.); [email protected] (R.D.G.) 3 Department of Cardiovascular Sciences, Anesthesia, Critical Care and Pain Management, University of Leicester, Leicester LE1 7RH, UK; [email protected] 4 Technopole of Ferrara, LTTA Laboratory for Advanced Therapies, 44122 Ferrara, Italy * Correspondence: [email protected] Academic Editor: Helmut Schmidhammer Received: 23 July 2020; Accepted: 23 August 2020; Published: 25 August 2020 Abstract: Opioids such as morphine—acting at the mu opioid receptor—are the mainstay for treatment of moderate to severe pain and have good efficacy in these indications. However, these drugs produce a plethora of unwanted adverse effects including respiratory depression, constipation, immune suppression and with prolonged treatment, tolerance, dependence and abuse liability. Studies in β-arrestin 2 gene knockout (βarr2( / )) animals indicate that morphine analgesia is potentiated − − while side effects are reduced, suggesting that drugs biased away from arrestin may manifest with a reduced-side-effect profile. However, there is controversy in this area with improvement of morphine-induced constipation and reduced respiratory effects in βarr2( / ) mice. Moreover, − − studies performed with mice genetically engineered with G-protein-biased mu receptors suggested increased sensitivity of these animals to both analgesic actions and side effects of opioid drugs.
    [Show full text]
  • Summary Analgesics Dec2019
    Status as of December 31, 2019 UPDATE STATUS: N = New, A = Advanced, C = Changed, S = Same (No Change), D = Discontinued Update Emerging treatments for acute and chronic pain Development Status, Route, Contact information Status Agent Description / Mechanism of Opioid Function / Target Indication / Other Comments Sponsor / Originator Status Route URL Action (Y/No) 2019 UPDATES / CONTINUING PRODUCTS FROM 2018 Small molecule, inhibition of 1% diacerein TWi Biotechnology / caspase-1, block activation of 1 (AC-203 / caspase-1 inhibitor Inherited Epidermolysis Bullosa Castle Creek Phase 2 No Topical www.twibiotech.com NLRP3 inflamasomes; reduced CCP-020) Pharmaceuticals IL-1beta and IL-18 Small molecule; topical NSAID Frontier 2 AB001 NSAID formulation (nondisclosed active Chronic low back pain Phase 2 No Topical www.frontierbiotech.com/en/products/1.html Biotechnologies ingredient) Small molecule; oral uricosuric / anti-inflammatory agent + febuxostat (xanthine oxidase Gout in patients taking urate- Uricosuric + 3 AC-201 CR inhibitor); inhibition of NLRP3 lowering therapy; Gout; TWi Biotechnology Phase 2 No Oral www.twibiotech.com/rAndD_11 xanthine oxidase inflammasome assembly, reduced Epidermolysis Bullosa Simplex (EBS) production of caspase-1 and cytokine IL-1Beta www.arraybiopharma.com/our-science/our-pipeline AK-1830 Small molecule; tropomyosin Array BioPharma / 4 TrkA Pain, inflammation Phase 1 No Oral www.asahi- A (ARRY-954) receptor kinase A (TrkA) inhibitor Asahi Kasei Pharma kasei.co.jp/asahi/en/news/2016/e160401_2.html www.neurosmedical.com/clinical-research;
    [Show full text]
  • The Main Tea Eta a El Mattitauli Mali Malta
    THE MAIN TEA ETA USA 20180169172A1EL MATTITAULI MALI MALTA ( 19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2018 /0169172 A1 Kariman (43 ) Pub . Date : Jun . 21 , 2018 ( 54 ) COMPOUND AND METHOD FOR A61K 31/ 437 ( 2006 .01 ) REDUCING APPETITE , FATIGUE AND PAIN A61K 9 / 48 (2006 .01 ) (52 ) U . S . CI. (71 ) Applicant : Alexander Kariman , Rockville , MD CPC . .. .. .. .. A61K 36 / 74 (2013 .01 ) ; A61K 9 / 4825 (US ) (2013 . 01 ) ; A61K 31/ 437 ( 2013 . 01 ) ; A61K ( 72 ) Inventor: Alexander Kariman , Rockville , MD 31/ 4375 (2013 .01 ) (US ) ( 57 ) ABSTRACT The disclosed invention generally relates to pharmaceutical (21 ) Appl . No. : 15 /898 , 232 and nutraceutical compounds and methods for reducing appetite , muscle fatigue and spasticity , enhancing athletic ( 22 ) Filed : Feb . 16 , 2018 performance , and treating pain associated with cancer, trauma , medical procedure , and neurological diseases and Publication Classification disorders in subjects in need thereof. The disclosed inven ( 51 ) Int. Ci. tion further relates to Kratom compounds where said com A61K 36 / 74 ( 2006 .01 ) pound contains at least some pharmacologically inactive A61K 31/ 4375 ( 2006 .01 ) component. pronuPatent Applicationolan Publication manu saJun . decor21, 2018 deSheet les 1 of 5 US 2018 /0169172 A1 reta Mitragynine 7 -OM - nitragynine *** * *momoda W . 00 . Paynantheine Speciogynine **** * * * ! 1000 co Speclociliatine Corynartheidine Figure 1 Patent Application Publication Jun . 21, 2018 Sheet 2 of 5 US 2018 /0169172 A1
    [Show full text]
  • The Utilization of Mu-Opioid Receptor Biased Agonists: Oliceridine, an Opioid Analgesic with Reduced Adverse Effects
    Current Pain and Headache Reports (2019) 23: 31 https://doi.org/10.1007/s11916-019-0773-1 HOT TOPICS IN PAIN AND HEADACHE (N. ROSEN, SECTION EDITOR) The Utilization of Mu-Opioid Receptor Biased Agonists: Oliceridine, an Opioid Analgesic with Reduced Adverse Effects Ivan Urits1 & Omar Viswanath2,3,4 & Vwaire Orhurhu1 & Kyle Gress5 & Karina Charipova5 & Alan D. Kaye6 & Anh Ngo1 Published online: 18 March 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Purpose of Review The purpose of this review is to summarize the current understanding of opioid pathways in mediating and/or modulating analgesia and adverse effects. Oliceridine is highlighted as a novel mu-opioid receptor agonist with selective activation of G protein and β-arrestin signaling pathways. Recent Findings Oliceridine (TRV130; [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9- yl]ethyl})amine) is a novel MOR agonist that selectively activates G protein and β-arrestin signaling pathways. A growing body of evidence suggests that compared to existing MOR agonists, Oliceridine and other G protein-selective modulators may produce therapeutic analgesic effects with reduced adverse effects. Summary Oliceridine provides analgesic benefits of a pure opioid agonist while limiting related adverse effects mediated through the β-arrestin pathway. Recent insights into the function and structure of G protein-coupled receptors has led to the development of novel analgesic therapies. Keywords Oliceridine . TRV130 . G protein-coupled receptors (GPCR) . Partial opioid agonists Introduction significant driver in an effort to develop novel opioid pharma- cotherapies with less adverse side effects.
    [Show full text]
  • Wednesday, June 12, 2019 4:00Pm
    Wednesday, June 12, 2019 4:00pm Oklahoma Health Care Authority 4345 N. Lincoln Blvd. Oklahoma City, OK 73105 The University of Oklahoma Health Sciences Center COLLEGE OF PHARMACY PHARMACY MANAGEMENT CONSULTANTS MEMORANDUM TO: Drug Utilization Review (DUR) Board Members FROM: Melissa Abbott, Pharm.D. SUBJECT: Packet Contents for DUR Board Meeting – June 12, 2019 DATE: June 5, 2019 Note: The DUR Board will meet at 4:00pm. The meeting will be held at 4345 N. Lincoln Blvd. Enclosed are the following items related to the June meeting. Material is arranged in order of the agenda. Call to Order Public Comment Forum Action Item – Approval of DUR Board Meeting Minutes – Appendix A Update on Medication Coverage Authorization Unit/Use of Angiotensin Converting Enzyme Inhibitor (ACEI)/ Angiotensin Receptor Blocker (ARB) Therapy in Patients with Diabetes and Hypertension (HTN) Mailing Update – Appendix B Action Item – Vote to Prior Authorize Aldurazyme® (Laronidase) and Naglazyme® (Galsulfase) – Appendix C Action Item – Vote to Prior Authorize Plenvu® [Polyethylene Glycol (PEG)-3350/Sodium Ascorbate/Sodium Sulfate/Ascorbic Acid/Sodium Chloride/Potassium Chloride] – Appendix D Action Item – Vote to Prior Authorize Consensi® (Amlodipine/Celecoxib) and Kapspargo™ Sprinkle [Metoprolol Succinate Extended-Release (ER)] – Appendix E Action Item – Vote to Update the Prior Authorization Criteria For H.P. Acthar® Gel (Repository Corticotropin Injection) – Appendix F Action Item – Vote to Prior Authorize Fulphila® (Pegfilgrastim-jmdb), Nivestym™ (Filgrastim-aafi),
    [Show full text]
  • State of the Art Opioid-Sparing Strategies for Post-Operative Pain in Adult Surgical Patients
    UC San Diego UC San Diego Previously Published Works Title State of the art opioid-sparing strategies for post-operative pain in adult surgical patients. Permalink https://escholarship.org/uc/item/3z9800kv Journal Expert opinion on pharmacotherapy, 20(8) ISSN 1465-6566 Authors Gabriel, Rodney A Swisher, Matthew W Sztain, Jacklynn F et al. Publication Date 2019-06-01 DOI 10.1080/14656566.2019.1583743 Peer reviewed eScholarship.org Powered by the California Digital Library University of California EXPERT OPINION ON PHARMACOTHERAPY https://doi.org/10.1080/14656566.2019.1583743 REVIEW State of the art opioid-sparing strategies for post-operative pain in adult surgical patients Rodney A. Gabriela,b,c, Matthew W. Swishera,c, Jacklynn F. Sztaina, Timothy J. Furnisha, Brian M. Ilfelda,c and Engy T. Saida aDepartment of Anesthesiology, Division of Regional Anesthesia and Acute Pain, University of California, San Diego, La Jolla, CA, USA; bDivision of Biomedical Informatics, University of California, San Diego, La Jolla, CA, USA; cOutcomes Research Consortium, Cleveland, OH, USA ABSTRACT ARTICLE HISTORY Introduction: There are various important implications associated with poorly controlled postoperative Received 17 October 2018 pain in the adult surgical patient – this includes cardiopulmonary complications, opioid-related side Accepted 13 February 2019 effects, unplanned hospital admissions, prolonged hospital stay, and the subsequent development of KEYWORDS chronic pain or opioid addiction. With the ongoing national opioid crisis, it is imperative that perio- Multimodal analgesia; acute perative providers implement pathways for surgical patients that reduce opioid requirements and pain- pain service; opioid; related complications. perioperative Areas covered: In this review, the authors discuss the components of a multimodal opioid-sparing analgesia pathway as it pertains to the perioperative environment.
    [Show full text]
  • Biased Agonism of Clinically Approved Μ-Opioid Receptor Agonists and TRV130 Is Not Controlled by Binding and Signaling Kinetics
    Biased agonism of clinically approved mu-opioid receptor agonists and TRV130 is not controlled by binding and signaling kinetics Pedersen, Mie Fabricius; Wrobel, Tomasz Marcin; Märcher-Rørsted, Emil; Pedersen, Daniel Sejer; Møller, Thor Christian; Gabriele, Federica; Pedersen, Henrik; Matosiuk, Dariusz; Foster, Simon Richard; Bouvier, Michel; Bräuner-Osborne, Hans Published in: Neuropharmacology DOI: 10.1016/j.neuropharm.2019.107718 Publication date: 2020 Document version Publisher's PDF, also known as Version of record Document license: CC BY Citation for published version (APA): Pedersen, M. F., Wrobel, T. M., Märcher-Rørsted, E., Pedersen, D. S., Møller, T. C., Gabriele, F., Pedersen, H., Matosiuk, D., Foster, S. R., Bouvier, M., & Bräuner-Osborne, H. (2020). Biased agonism of clinically approved mu-opioid receptor agonists and TRV130 is not controlled by binding and signaling kinetics. Neuropharmacology, 166, [107718]. https://doi.org/10.1016/j.neuropharm.2019.107718 Download date: 01. okt.. 2021 Neuropharmacology 166 (2020) 107718 Contents lists available at ScienceDirect Neuropharmacology journal homepage: www.elsevier.com/locate/neuropharm Biased agonism of clinically approved μ-opioid receptor agonists and T TRV130 is not controlled by binding and signaling kinetics Mie Fabricius Pedersena,b, Tomasz Marcin Wróbela,c, Emil Märcher-Rørsteda, Daniel Sejer Pedersena, Thor Christian Møllera, Federica Gabrielea, Henrik Pedersend, ∗ ∗∗ Dariusz Matosiukc, Simon Richard Fostera, Michel Bouvierb, , Hans Bräuner-Osbornea, a Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark b Department of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, QC, Canada c Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Medical University of Lublin, Lublin, Poland d Lundbeck A/S, Valby, Denmark HIGHLIGHTS • Oliceridine ((R)-TRV130) and buprenorphine display equal extreme biased agonism.
    [Show full text]
  • IV Oliceridine for the Management of Moderate-To-Severe Acute Pain in Hospital Or Controlled Clinical Settings
    CO-1 IV Oliceridine for the Management of Moderate-to-Severe Acute Pain in Hospital or Controlled Clinical Settings October 11, 2018 Trevena, Inc. Meeting of the Anesthetic and Analgesic Drugs Products Advisory Committee CO-2 Introduction Maxine Gowen, PhD Founding President and CEO Trevena, Inc. CO-3 Overview of IV Oliceridine for Management of Moderate-to-Severe Acute Pain ◼ New chemical entity with novel mechanism of action ◼ Designed to deliver pain relief of conventional IV opioid with fewer opioid-related adverse events (ORAEs) ▪ Improving benefit-risk profile for patients ◼ First new opioid molecule in decades CO-4 Oliceridine Scientific History ◼ Trevena founded in 2008 to translate G Protein-Coupled Receptor GPCR discoveries into better medicines (GPCR) ◼ Lab of Robert Lefkowitz, Duke University ▪ 2012 Nobel Prize in Chemistry for work on GPCRs CO-5 Prior Theory on GPCRs, Including µ-Opioid Receptor ◼ Operated like light switch ▪ ON by agonist like morphine ▪ OFF by antagonists like naloxone ◼ Beneficial and adverse effects inseparable ◼ Opioid analgesia only obtained with associated ORAEs CO-6 New Hypothesis: GPCRs Have Distinct Signaling Pathways Conventional Opioids Oliceridine µ-opioid µ-opioid receptor receptor Cell surface Cell surface G Cell interior G Cell interior protein protein β-arrestin β-arrestin Analgesia Hypothesis (vs Conventional Opioids): Similar Analgesia Respiratory Depression Respiratory Depression ▪ ▪ Similar Liking / Dependence Nausea / Vomiting Nausea / Vomiting Liking / Dependence ▪ Less Respiratory
    [Show full text]
  • Activation of M-D Opioid Receptor Heteromers Inhibits Neuropathic Pain Behavior in Rodents
    Research Paper Activation of m-d opioid receptor heteromers inhibits neuropathic pain behavior in rodents Vinod Tiwaria, Shao-Qiu Hea, Qian Huanga, Lingli Lianga, Fei Yanga, Zhiyong Chena, Vineeta Tiwaria, Wakako Fujitab, Lakshmi A. Devib, Xinzhong Dongc,d, Yun Guana,e, Srinivasa N. Rajaa,* 10/27/2020 on Lc+LFovvA8kwLlXep+KVmBVRPo9c/w+jP3jM+VLppt6EIGY6AvlsMLr0U4h2Wl4ClQhoxQwnxSxh7PCm3iIk+ncF1wL2pK61fHxkxqEG1VREkSDLiG2Pu36FVfirG5EBAMD/bDeF43o= by http://journals.lww.com/pain from Downloaded Downloaded from Abstract http://journals.lww.com/pain Several reports support the idea that m- and d-opioid receptors (ORs) may exist as heterodimers in brain regions involved in pain signaling. The unique pharmacology of these heteromers may present a novel analgesic target. However, the role of m-d heteromers in sensory neurons involved in pain and opioid analgesia remains unclear, particularly during neuropathic pain. We examined the effects of spinal nerve injury on m-d heteromer expression in dorsal root ganglion (DRG) neurons and the effects of a m-d by heteromer–targeting agonist, CYM51010, on neuropathic pain behavior in rats and mice. An L5 spinal nerve ligation (SNL) in rats Lc+LFovvA8kwLlXep+KVmBVRPo9c/w+jP3jM+VLppt6EIGY6AvlsMLr0U4h2Wl4ClQhoxQwnxSxh7PCm3iIk+ncF1wL2pK61fHxkxqEG1VREkSDLiG2Pu36FVfirG5EBAMD/bDeF43o= significantly decreased m-d heteromer expression in L5 DRG but increased heteromer levels in uninjured L4 DRG. Importantly, in SNL rats, subcutaneous injection of CYM51010 inhibited mechanical hypersensitivity in a dose-related manner (EC50: 1.09 mg/kg) and also reversed heat hyperalgesia and attenuated ongoing pain (2 mg/kg, subcutaneously). HEK-293T cell surface-labeled with m- and d-ORs internalized both receptors after exposure to CYM51010. By contrast, in cells transfected with m-OR alone, CYM51010 was significantly less effective at inducing receptor internalization.
    [Show full text]
  • Laws 2021, LB236, § 4
    LB236 LB236 2021 2021 LEGISLATIVE BILL 236 Approved by the Governor May 26, 2021 Introduced by Brewer, 43; Clements, 2; Erdman, 47; Slama, 1; Lindstrom, 18; Murman, 38; Halloran, 33; Hansen, B., 16; McDonnell, 5; Briese, 41; Lowe, 37; Groene, 42; Sanders, 45; Bostelman, 23; Albrecht, 17; Dorn, 30; Linehan, 39; Friesen, 34; Aguilar, 35; Gragert, 40; Kolterman, 24; Williams, 36; Brandt, 32. A BILL FOR AN ACT relating to law; to amend sections 28-1202 and 69-2436, Reissue Revised Statutes of Nebraska, and sections 28-401 and 28-405, Revised Statutes Cumulative Supplement, 2020; to redefine terms, change drug schedules, and adopt federal drug provisions under the Uniform Controlled Substances Act; to provide an exception to the offense of carrying a concealed weapon as prescribed; to define a term; to change provisions relating to renewal of a permit to carry a concealed handgun; to provide a duty for the Nebraska State Patrol; to eliminate an obsolete provision; to harmonize provisions; and to repeal the original sections. Be it enacted by the people of the State of Nebraska, Section 1. Section 28-401, Revised Statutes Cumulative Supplement, 2020, is amended to read: 28-401 As used in the Uniform Controlled Substances Act, unless the context otherwise requires: (1) Administer means to directly apply a controlled substance by injection, inhalation, ingestion, or any other means to the body of a patient or research subject; (2) Agent means an authorized person who acts on behalf of or at the direction of another person but does not include a common or contract carrier, public warehouse keeper, or employee of a carrier or warehouse keeper; (3) Administration means the Drug Enforcement Administration of the United States Department of Justice; (4) Controlled substance means a drug, biological, substance, or immediate precursor in Schedules I through V of section 28-405.
    [Show full text]
  • Replacement of Current Opioid Drugs Focusing on MOR-Related Strategies
    JPT-107519; No of Pages 17 Pharmacology & Therapeutics xxx (2020) xxx Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Replacement of current opioid drugs focusing on MOR-related strategies Jérôme Busserolles a,b, Stéphane Lolignier a,b, Nicolas Kerckhove a,b,c, Célian Bertin a,b,c, Nicolas Authier a,b,c, Alain Eschalier a,b,⁎ a Université Clermont Auvergne, INSERM, CHU, NEURO-DOL Pharmacologie Fondamentale et Clinique de la douleur, F-63000 Clermont-Ferrand, France b Institut ANALGESIA, Faculté de Médecine, F-63000 Clermont-Ferrand, France c Observatoire Français des Médicaments Antalgiques (OFMA), French monitoring centre for analgesic drugs, CHU, F-63000 Clermont-Ferrand, France article info abstract Available online xxxx The scarcity and limited risk/benefit ratio of painkillers available on the market, in addition to the opioid crisis, warrant reflection on new innovation strategies. The pharmacopoeia of analgesics is based on products that are often old and derived from clinical empiricism, with limited efficacy or spectrum of action, or resulting in Keywords: an unsatisfactory tolerability profile. Although they are reference analgesics for nociceptive pain, opioids are sub- Analgesia ject to the same criticism. The use of opium as an analgesic is historical. Morphine was synthesized at the begin- Mu opioid receptors (MORs) ning of the 19th century. The efficacy of opioids is limited in certain painful contexts and these drugs can induce Opioid adverse side effects potentially serious and fatal adverse effects. The current North American opioid crisis, with an ever-rising number Opioid abuse and misuse of deaths by opioid overdose, is a tragic illustration of this.
    [Show full text]