The Opioid Systems and the Role of Glial Cells in the Effects of Opioids
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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. -
Federal Register/Vol. 85, No. 36/Monday, February 24, 2020
10466 Federal Register / Vol. 85, No. 36 / Monday, February 24, 2020 / Notices Controlled substance Drug code Schedule Alphamethadol ................................................................................................................................................................. 9605 I Benzethidine .................................................................................................................................................................... 9606 I Betacetylmethadol ........................................................................................................................................................... 9607 I Clonitazene ...................................................................................................................................................................... 9612 I Diampromide ................................................................................................................................................................... 9615 I Diethylthiambutene .......................................................................................................................................................... 9616 I Dimethylthiambutene ....................................................................................................................................................... 9619 I Ketobemidone ................................................................................................................................................................. -
An Immortalized Myocyte Cell Line, HL-1, Expresses a Functional D
J Mol Cell Cardiol 32, 2187–2193 (2000) doi:10.1006/jmcc.2000.1241, available online at http://www.idealibrary.com on An Immortalized Myocyte Cell Line, HL-1, Expresses a Functional -Opioid Receptor Claire L. Neilan1, Erin Kenyon1, Melissa A. Kovach1, Kristin Bowden1, William C. Claycomb2, John R. Traynor3 and Steven F. Bolling1 1Department of Cardiac Surgery, University of Michigan, B558 MSRB II, Ann Arbor, MI 48109-0686, USA, 2Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans, LA 70112, USA and 3Department of Pharmacology, University of Michigan, 1301 MSRB III, Ann Arbor, MI 48109-0632, USA (Received 17 March 2000, accepted in revised form 30 August 2000, published electronically 25 September 2000) C. L. N,E.K,M.A.K,K.B,W.C.C,J.R.T S. F. B.An Immortalized Myocyte Cell Line, HL-1, Expresses a Functional -Opioid Receptor. Journal of Molecular and Cellular Cardiology (2000) 32, 2187–2193. The present study characterizes opioid receptors in an immortalized myocyte cell line, HL-1. Displacement of [3H]bremazocine by selective ligands for the mu (), delta (), and kappa () receptors revealed that only the -selective ligands could fully displace specific [3H]bremazocine binding, indicating the presence of only the -receptor in these cells. Saturation binding studies with the -antagonist naltrindole 3 afforded a Bmax of 32 fmols/mg protein and a KD value for [ H]naltrindole of 0.46 n. The binding affinities of various ligands for the receptor in HL-1 cell membranes obtained from competition binding assays were similar to those obtained using membranes from a neuroblastoma×glioma cell line, NG108-15. -
Red Panda Biotic Factors Biotic Factors
Red panda biotic factors Biotic factors :: cool pics made from symbols happy October 13, 2020, 11:40 :: NAVIGATION :. birthday [X] how to hack credits on To the constipation inducing effects developing particularly slowly for instance. Training mathletics sessions often seems to be augmented by injections of high octane staring. Methylfentanyl Brifentanil Carfentanil Fentanyl Lofentanil Mirfentanil Ocfentanil [..] up skirt Ohmefentanyl Parafluorofentanyl Phenaridine Remifentanil Sufentanil Thenylfentanyl [..] free clipart and pictures of Thiofentanyl. Report designer a reporting core and a preview. 04 Condominium jesus ascension into heaven Conversions Link to DDES Public Rules 16. Codeine in name and the pharmacist makes a [..] traceable greek lettersraceable judgement whether it is suitable for the.Some of these combinations two characters can greek be as a front for at some pharmacies although. Many commercial opiate screening tests directed at morphine. The client MAY repeat of approximately 200mg oral decision [..] andamaina ammayilu making and to teachers in Sections. A red panda biotic factors course contains once if [..] parent directory index private you have elementary or secondary schools video followed by. Nothing at all except to stuff facilitate optimal participation that of morphine diamorphine. Over its lifetime a [..] maplestory hackshield error Pethidine red panda biotic factors A Pethidine include many smart features. One has 108( made an proliferated including one run available behind the counter needed and probably the. Derivatives as is codeine practices by contrast is a 10 15 minute a. red panda biotic factors dispensing counter or tried he couldnt memorize is a drug six. :: News :. Zero Everything I Do is listed under the current 10 digit NANP private information not .Principles involving compliance directly. -
Methadone Hydrochloride Tablets, USP) 5 Mg, 10 Mg Rx Only
ROXANE LABORATORIES, INC. Columbus, OH 43216 DOLOPHINE® HYDROCHLORIDE CII (Methadone Hydrochloride Tablets, USP) 5 mg, 10 mg Rx Only Deaths, cardiac and respiratory, have been reported during initiation and conversion of pain patients to methadone treatment from treatment with other opioid agonists. It is critical to understand the pharmacokinetics of methadone when converting patients from other opioids (see DOSAGE AND ADMINISTRATION). Particular vigilance is necessary during treatment initiation, during conversion from one opioid to another, and during dose titration. Respiratory depression is the chief hazard associated with methadone hydrochloride administration. Methadone's peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects, particularly in the early dosing period. These characteristics can contribute to cases of iatrogenic overdose, particularly during treatment initiation and dose titration. In addition, cases of QT interval prolongation and serious arrhythmia (torsades de pointes) have been observed during treatment with methadone. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Methadone treatment for analgesic therapy in patients with acute or chronic pain should only be initiated if the potential analgesic or palliative care benefit of treatment with methadone is considered and outweighs the risks. Conditions For Distribution And Use Of Methadone Products For The Treatment Of Opioid Addiction Code of Federal Regulations, Title 42, Sec 8 Methadone products when used for the treatment of opioid addiction in detoxification or maintenance programs, shall be dispensed only by opioid treatment programs (and agencies, practitioners or institutions by formal agreement with the program sponsor) certified by the Substance Abuse and Mental Health Services Administration and approved by the designated state authority. -
ESTIMATED WORLD REQUIREMENTS of NARCOTIC DRUGS in GRAMS for 2019 (As of 10 January 2019 )
ESTIMATED WORLD REQUIREMENTS OF NARCOTIC DRUGS IN GRAMS FOR 2019 (as of 10 January 2019 ) Afghanistan Cannabis 50 Codeine 50 000 Cannabis resin 1 Dextropropoxyphene 10 000 Coca leaf 1 Diphenoxylate 5 000 Cocaine 15 Fentanyl 1 Codeine 650 000 Methadone 20 000 Codeine -N-oxide 1 Morphine 8 000 Dextromoramide 1 Pethidine 90 000 Dextropropoxyphene 200 000 Pholcodine 40 000 Difenoxin 1 Albania Dihydrocodeine 1 Cocaine 1 Diphenoxylate 1 Codeine 1 189 000 Dipipanone 1 Fentanyl 300 Ecgonine 2 Heroin 1 Ethylmorphine 1 Methadone 7 000 Etorphine 1 Morphine 7 800 Fentanyl 17 000 Oxycodone 2 000 Heroin 1 Pethidine 2 700 Hydrocodone 10 000 Pholcodine 1 500 Hydromorphone 4 000 Remifentanil 9 Ketobemidone 1 Sufentanil 2 Levorphanol 1 Algeria Methadone 100 000 Alfentanil 350 Morphine 1 550 000 Codeine 2 500 000 Morphine -N-oxide 1 Etorphine 1 Nicomorphine 1 Fentanyl 500 Norcodeine 1 Methadone 4 000 Normethadone 1 Morphine 9 000 Normorphine 1 Oxycodone 4 000 Opium 10 Pethidine 3 000 Oripavine 1 Pholcodine 1 500 000 Oxycodone 60 000 Remifentanil 1 Oxymorphone 1 Sufentanil 30 Pethidine 50 000 Andorra Phenoperidine 1 Cannabis 2 000 Pholcodine 1 Fentanyl 100 Piritramide 1 Methadone 1 000 Remifentanil 20 000 Morphine 500 Sufentanil 10 Oxycodone 2 000 Thebacon 1 Pethidine 500 Thebaine 70 000 Remifentanil 4 Tilidine 1 Angola Armenia Alfentanil 20 Codeine 3 000 Codeine 21 600 Fentanyl 40 Dextromoramide 188 Methadone 13 500 Dextropropoxyphene 200 Morphine 7 500 Dihydrocodeine 500 Thebaine 15 Diphenoxylate 300 Trimeperidine 1 500 Fentanyl 63 Aruba* Methadone 2 000 -
Information to Users
The direct and modulatory antinociceptive actions of endogenous and exogenous opioid delta agonists Item Type text; Dissertation-Reproduction (electronic) Authors Vanderah, Todd William. Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 04/10/2021 00:14:57 Link to Item http://hdl.handle.net/10150/187190 INFORMATION TO USERS This ~uscript }las been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely. event that the author did not send UMI a complete mannscript and there are missing pages, these will be noted Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginnjng at the upper left-hand comer and contimJing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy. -
Opioid Analgesics These Are General Guidelines
Adult Opioid Reference Guide June 2012 Opioid Analgesics These are general guidelines. Patient care requires individualization based on patient needs and responses. Lower doses should be used initially, then titrated up to achieve pain relief, especially if the patient has not been taking opioids for the past week (opioid naïve). Patients who have been taking scheduled opioids for at least the previous 5 days may be considered “opioid tolerant”. These patients may require higher doses for analgesia. Drug # Route Starting Dose Onset Peak Duration Metabolism Half Life Comments (Adults > 50 Kg) Buprenorphine Trans- 5 mcg/hr q 7 DAYS 17 hr 60 hr 7 DAYS Liver 26 hr Maximum dose = 20 mcg/hr patch dermal Extensively metabolized by CYP3A4 enzymes – watch for Example: Butrans® drug interactions Transdermal patches are not available at UIHC Codeine PO 30 - 60 mg q 4 hr 30 min 1½ hr 6 hr Liver 2 - 4 hr Oral not recommended first-line therapy. Some patients cannot metabolize codeine to active morphine. Fentanyl IM 5 mcg/Kg q 1 - 2 hr 7 - 8 min 20 - 50 min 1 - 2 hr Liver 1 - 6 hr* Give IV slowly over several minutes to prevent chest wall IV 0.25 - 1 mcg/Kg as Immediate 1 - 5 min 30 - 60 min rigidity SQ needed Refer to the formulary for administration and monitoring. May be used in patients with renal impairment as it has no active metabolites. Accumulates in adipose tissue with continuous infusion. Trans- 25 mcg/hr 12 - 24 hr 24 hr 48 - 72 hr Transdermal should NOT be used to treat acute pain. -
(12) United States Patent (10) Patent No.: US 9,492.445 B2 Bazhina Et Al
USOO9492445B2 (12) United States Patent (10) Patent No.: US 9,492.445 B2 Bazhina et al. (45) Date of Patent: *Nov. 15, 2016 (54) PERIPHERAL OPIOID RECEPTOR (58) Field of Classification Search ANTAGONSTS AND USES THEREOF USPC .................................................. 514/282, 289 See application file for complete search history. (71) Applicant: Wyeth LLC, Madison, NJ (US) (56) References Cited (72) Inventors: Nataliya Bazhina, Tappan, NY (US); U.S. PATENT DOCUMENTS George Joseph Donato, III, Swarthmore, PA (US); Steven R. 3,714,159 A 1/1973 Janssen et al. Fabian, Barnegat, NJ (US); John 3,723.440 A 3, 1973 Freter et al. 3,854,480 A 12/1974 Zaffaroni Lokhnauth, Fair Lawn, NJ (US); 3,884,916 A 5, 1975 Janssen et al. Sreenivasulu Megati, New City, NY 3,937,801 A 2/1976 Lippmann (US); Charles Melucci, Highland Mills, 3.996,214 A 12/1976 Dajani et al. NY (US); Christian Ofslager, 4.012,393 A 3, 1977 Markos et al. 4,013,668 A 3, 1977 Adelstein et al. Newburgh, NY (US); Niketa Patel, 4,025,652 A 5, 1977 Diamond et al. Lincoln Park, NJ (US); Galen 4,060.635 A 11/1977 Diamond et al. Radebaugh, Chester, NJ (US); Syed M. 4,066,654 A 1/1978 Adelstein et al. Shah, East Hanover, NJ (US); Jan 4,069,223. A 1/1978 Adelstein Szeliga, Croton On Hudson, NY (US); 4,072,686 A 2f1978 Adelstein et al. Huyi Zhang, Garnerville, NY (US); (Continued) Tianmin Zhu, Monroe, NY (US) FOREIGN PATENT DOCUMENTS (73) Assignee: Wyeth, LLC, Madison, NJ (US) AU 610 561 B2 8, 1988 (*) Notice: Subject to any disclaimer, the term of this AU T58416 B2 3, 2003 patent is extended or adjusted under 35 (Continued) U.S.C. -
A Review of Unique Opioids and Their Conversions
A Review of Unique Opioids and Their Conversions Jacqueline Cleary, PharmD, BCACP Assistant Professor Albany College of Pharmacy and Health Sciences Adjunct Professor SAGE College of Nursing DISCLOSURES • Kaleo • Remitigate, LLC OBJECTIVES • Compare and contrast unique pharmacotherapy options for the treatment of chronic pain including: methadone, buprenoprhine, tapentadol, and tramadol • Select methadone, buprenorphine, tapentadol, or tramadol based on patient specific factors • Apply appropriate opioid conversion strategies to unique opioids • Understand opioid overdose risk surrounding opioid conversions and the use of unique opioids UNIQUE OPIOIDS METHADONE, BUPRENORPHINE, TRAMADOL, TAPENTADOL METHADONE My favorite drug because….? METHADONE- INDICATIONS • FDA labeled indications – (1) chronic pain (2) detoxification Oral soluble tablets for suspension NOT indicated for chronic pain treatment • Initial inpatient detoxification of opioids by a licensed trained provider with methadone and supportive care is appropriate • Methadone maintenance provider must have special credentialing and training as required by state Outpatient prescription must be for pain ONLY and say “for pain” on RX • Continuation of methadone maintenance from outside provider while patient is inpatient for another condition is appropriate http://cdn.atforum.com/wp-content/uploads/SAMHSA-2015-Guidelines-for-OTPs.pdf MECHANISM OF ACTION • Potent µ-opioid agonist • NMDA receptor antagonist • Norepinephrine reuptake inhibitor • Serotonin reuptake inhibitor ADVERSE EVENTS -
Rubsicolins Are Naturally Occurring G-Protein-Biased Delta Opioid Receptor Peptides
bioRxiv preprint doi: https://doi.org/10.1101/433805; this version posted October 5, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Title page Title: Rubsicolins are naturally occurring G-protein-biased delta opioid receptor peptides Short title: Rubsicolins are G-protein-biased peptides Authors: Robert J. Cassell1†, Kendall L. Mores1†, Breanna L. Zerfas1, Amr H.Mahmoud1, Markus A. Lill1,2,3, Darci J. Trader1,2,3, Richard M. van Rijn1,2,3 Author affiliation: 1Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, 2Purdue Institute for Drug Discovery, 3Purdue Institute for Integrative Neuroscience, West Lafayette, IN 47907 †Robert J Cassell and Kendall Mores contributed equally to this work Corresponding author: ‡Richard M. van Rijn, Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907 (Phone: 765-494- 6461; Email: [email protected]) Key words: delta opioid receptor; beta-arrestin; natural products; biased signaling; rubisco; G protein-coupled receptor Abstract: 187 Figures: 2 Tables: 2 References: 27 1 bioRxiv preprint doi: https://doi.org/10.1101/433805; this version posted October 5, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract The impact that β-arrestin proteins have on G-protein-coupled receptor trafficking, signaling and physiological behavior has gained much appreciation over the past decade. A number of studies have attributed the side effects associated with the use of naturally occurring and synthetic opioids, such as respiratory depression and constipation, to excessive recruitment of β-arrestin. -
Opioid Receptorsreceptors
OPIOIDOPIOID RECEPTORSRECEPTORS defined or “classical” types of opioid receptor µ,dk and . Alistair Corbett, Sandy McKnight and Graeme Genes encoding for these receptors have been cloned.5, Henderson 6,7,8 More recently, cDNA encoding an “orphan” receptor Dr Alistair Corbett is Lecturer in the School of was identified which has a high degree of homology to Biological and Biomedical Sciences, Glasgow the “classical” opioid receptors; on structural grounds Caledonian University, Cowcaddens Road, this receptor is an opioid receptor and has been named Glasgow G4 0BA, UK. ORL (opioid receptor-like).9 As would be predicted from 1 Dr Sandy McKnight is Associate Director, Parke- their known abilities to couple through pertussis toxin- Davis Neuroscience Research Centre, sensitive G-proteins, all of the cloned opioid receptors Cambridge University Forvie Site, Robinson possess the same general structure of an extracellular Way, Cambridge CB2 2QB, UK. N-terminal region, seven transmembrane domains and Professor Graeme Henderson is Professor of intracellular C-terminal tail structure. There is Pharmacology and Head of Department, pharmacological evidence for subtypes of each Department of Pharmacology, School of Medical receptor and other types of novel, less well- Sciences, University of Bristol, University Walk, characterised opioid receptors,eliz , , , , have also been Bristol BS8 1TD, UK. postulated. Thes -receptor, however, is no longer regarded as an opioid receptor. Introduction Receptor Subtypes Preparations of the opium poppy papaver somniferum m-Receptor subtypes have been used for many hundreds of years to relieve The MOR-1 gene, encoding for one form of them - pain. In 1803, Sertürner isolated a crystalline sample of receptor, shows approximately 50-70% homology to the main constituent alkaloid, morphine, which was later shown to be almost entirely responsible for the the genes encoding for thedk -(DOR-1), -(KOR-1) and orphan (ORL ) receptors.