Fentanyl Family at the Mu-Opioid Receptor: Uniform Assessment of Binding and Computational Analysis
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Evaluation of in Silico Approach for Prediction of Presence of Opioid Peptides in Wheat
Evaluation of in silico approach for prediction of presence of opioid peptides in wheat This is the Accepted version of the following publication Garg, Swati, Apostolopoulos, Vasso, Nurgali, Kulmira and Mishra, Vijay Kumar (2018) Evaluation of in silico approach for prediction of presence of opioid peptides in wheat. Journal of Functional Foods, 41. 34 - 40. ISSN 1756-4646 The publisher’s official version can be found at https://www.sciencedirect.com/science/article/pii/S1756464617307454 Note that access to this version may require subscription. Downloaded from VU Research Repository https://vuir.vu.edu.au/36577/ 1 1 Evaluation of in silico approach for prediction of presence of opioid peptides in wheat 2 gluten 3 Abstract 4 Opioid like morphine and codeine are used for the management of pain, but are associated 5 with serious side-effects limiting their use. Wheat gluten proteins were assessed for the 6 presence of opioid peptides on the basis of tyrosine and proline within their sequence. Eleven 7 peptides were identified and occurrence of predicted sequences or their structural motifs were 8 analysed using BIOPEP database and ranked using PeptideRanker. Based on higher peptide 9 ranking, three sequences YPG, YYPG and YIPP were selected for determination of opioid 10 activity by cAMP assay against µ and κ opioid receptors. Three peptides inhibited the 11 production of cAMP to varied degree with EC50 values of YPG, YYPG and YIPP were 5.3 12 mM, 1.5 mM and 2.9 mM for µ-opioid receptor, and 1.9 mM, 1.2 mM and 3.2 mM for κ- 13 opioid receptor, respectively. -
Differentiation and Identification of Fentanyl Analogues Using GC-IRD
Forensic Chemistry 20 (2020) 100255 Contents lists available at ScienceDirect Forensic Chemistry journal homepage: www.elsevier.com/locate/forc Diferentiation and identifcation of fentanyl analogues using GC-IRD T ⁎ ⁎ Agnes D. Winokura, , Lindsay M. Kaufmana, Jose R. Almirallb, a DEA Southeast Laboratory, Miami, FL, USA b Department of Chemistry and Biochemistry and Center for Advanced Research in Forensic Science (CARFS), Florida International University, Miami, FL, USA HIGHLIGHTS • Demonstration of the diferentiation and identifcation of fentanyls using GC-IRD. • Optimization of GC-IRD parameters including chromatographic and spectral acquisition. • Reporting of limitations in sensitivity for casework samples. • Case study description involving the use of GC-IRD for analysis of a polydrug mixture. ARTICLE INFO ABSTRACT Keywords: Fentanyl analogues and their positional isomers have similar chemical structural confgurations making them GC-IRD difcult to identify and diferentiate. Gas chromatography coupled to a gas-phase infrared detector (GC-IRD) is a Fentanyl analogues useful and powerful tool for the unambiguous identifcation of fentanyl compounds where traditional analytical PTV techniques such as gas chromatography–mass spectrometry (GC–MS) ofer limited information for this class of Light pipe compounds. In this study, we demonstrate the utility of GC-IRD and show how this complementary information Positional isomers enables the identifcation of fentanyl analogues (2- and 3- furanylfentanyl, 2-furanylbenzylfentanyl, croto- nylfentanyl, cyclopropylfentanyl, methoxyacetylfentanyl, carfentanil, meta-fuoroisobutyryl fentanyl, para- fuoroisobutyryl fentanyl and ortho-fuoroisobutyryl fentanyl) when combined with GC–MS data. A description of the operating conditions including how the optimization of GC-IRD parameters can enhance the spectral resolution and unambiguous identifcation of these fentanyl analogues is presented, for the frst time. -
English Advance Version of the CND Report
E/2020/28 E/CN.7/2020/15 United Nations Commission on Narcotic Drugs Report on the sixty-third session (13 December 2019 and 2–6 March 2020) Economic and Social Council Official Records, 2020 Supplement No. 8 Economic and Social Council E/2020/28 Official Records, 2020 E/CN.7/2020/15 Supplement No. 8 Commission on Narcotic Drugs Report on the sixty-third session (13 December 2019 and2–6 March 2020) United Nations • New York, 2020 E/2020/28 E/CN.7/2020/15 Note Symbols of United Nations documents are composed of letters combined with figures. Mention of such a symbol indicates a reference to a United Nations document. The report of the Commission on Narcotic Drugs on its reconvened sixty-third session, to be held on 3 and 4 December 2020, will be issued as Official Records of the Economic and Social Council, 2020, Supplement No. 8A (E/2020/28/Add.1). ISSN 0251-9941 E/2020/28 E/CN.7/2020/15 [23 March 2020] Contents Chapter Page Executive summary ......................................................... vi I. Matters calling for action by the Economic and Social Council or brought to its attention 1 A. Draft decisions for adoption by the Economic and Social Council ............... 1 I. Report of the Commission on Narcotic Drugs on its sixty-third session and provisional agenda for its sixty-fourth session ........................... 1 II. Report of the International Narcotics Control Board ...................... 2 B. Matters brought to the attention of the Economic and Social Council ............ 2 Resolution 63/1 Promoting efforts by Member States to address and counter the world drug problem, in particular supply reduction-related measures, through effective partnerships with private sector entities .............................................. -
Backing Material Packaging Liner
US009314527B2 (12) United States Patent (10) Patent No.: US 9,314,527 B2 Cottrell et al. (45) Date of Patent: *Apr. 19, 2016 (54) TRANSDERMAL DELIVERY PATCH 9/7061 (2013.01); A61K 9/7084 (2013.01); (71) Applicant: Phosphagenics Limited, Clayton, A61 K3I/355 (2013.01); A61K47/24 Victoria (AU) SE7 8E.O. (72) Inventors: Jeremy Cottrell, Caulfield South (AU); ( .01): ( .01): (2013.01) Giacinto Gaetano, South Melbourne (AU); Mahmoud El-Tamimy, Meadow (58) Field of Classification Search Heights (AU); Nicholas Kennedy, None Boronia (AU); Paul David Gavin, See application file for complete search history. Chadstone (AU) (56) References Cited (73) Assignee: Phosphagenics Limited, Victoria (AU) (*) Notice: Subject to any disclaimer, the term of this U.S. PATENT DOCUMENTS patent is extended or adjusted under 35 2,407,823. A 9, 1946 Fieser U.S.C. 154(b) by 0 days. 2.457,932 A 1/1949 Solmssen et al. This patent is Subject to a terminal dis- (Continued) claimer. (21) Appl. No.: 14/550,514 FOREIGN PATENT DOCUMENTS ppl. No.: 9 (22) Filed: Nov. 21, 2014 A 3.3 5.83 (65) Prior Publication Data (Continued) Related U.S. Application Data Gianello et al. Subchronic Oral Toxicity Study of Mixed Tocopheryl (63) Continuation of application No. 14/086,738, filed on Phosphates in Rates, International Journal of Toxicology, 26:475 Nov. 21, 2013, now abandoned, which is a 490; 2007.* continuation of application No. 13/501,500, filed as (Continued) application No. PCT/AU2011/000358 on Mar. 30, 2011, now Pat. No. 8,652,511. Primary Examiner — Robert A Wax (60) Provisional application No. -
Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017
Q UO N T FA R U T A F E BERMUDA PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 BR 111 / 2017 The Minister responsible for health, in exercise of the power conferred by section 48A(1) of the Pharmacy and Poisons Act 1979, makes the following Order: Citation 1 This Order may be cited as the Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017. Repeals and replaces the Third and Fourth Schedule of the Pharmacy and Poisons Act 1979 2 The Third and Fourth Schedules to the Pharmacy and Poisons Act 1979 are repealed and replaced with— “THIRD SCHEDULE (Sections 25(6); 27(1))) DRUGS OBTAINABLE ONLY ON PRESCRIPTION EXCEPT WHERE SPECIFIED IN THE FOURTH SCHEDULE (PART I AND PART II) Note: The following annotations used in this Schedule have the following meanings: md (maximum dose) i.e. the maximum quantity of the substance contained in the amount of a medicinal product which is recommended to be taken or administered at any one time. 1 PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 mdd (maximum daily dose) i.e. the maximum quantity of the substance that is contained in the amount of a medicinal product which is recommended to be taken or administered in any period of 24 hours. mg milligram ms (maximum strength) i.e. either or, if so specified, both of the following: (a) the maximum quantity of the substance by weight or volume that is contained in the dosage unit of a medicinal product; or (b) the maximum percentage of the substance contained in a medicinal product calculated in terms of w/w, w/v, v/w, or v/v, as appropriate. -
Recommended Methods for the Identification and Analysis of Fentanyl and Its Analogues in Biological Specimens
Recommended methods for the Identification and Analysis of Fentanyl and its Analogues in Biological Specimens MANUAL FOR USE BY NATIONAL DRUG ANALYSIS LABORATORIES Laboratory and Scientific Section UNITED NATIONS OFFICE ON DRUGS AND CRIME Vienna Recommended Methods for the Identification and Analysis of Fentanyl and its Analogues in Biological Specimens MANUAL FOR USE BY NATIONAL DRUG ANALYSIS LABORATORIES UNITED NATIONS Vienna, 2017 Note Operating and experimental conditions are reproduced from the original reference materials, including unpublished methods, validated and used in selected national laboratories as per the list of references. A number of alternative conditions and substitution of named commercial products may provide comparable results in many cases. However, any modification has to be validated before it is integrated into laboratory routines. ST/NAR/53 Original language: English © United Nations, November 2017. All rights reserved. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. Mention of names of firms and commercial products does not imply the endorse- ment of the United Nations. This publication has not been formally edited. Publishing production: English, Publishing and Library Section, United Nations Office at Vienna. Acknowledgements The Laboratory and Scientific Section of the UNODC (LSS, headed by Dr. Justice Tettey) wishes to express its appreciation and thanks to Dr. Barry Logan, Center for Forensic Science Research and Education, at the Fredric Rieders Family Founda- tion and NMS Labs, United States; Amanda L.A. -
Understanding and Challenging the Drugs: Chemistry and Toxicology
UNDERSTANDING AND CHALLENGING THE DRUGS: CHEMISTRY AND TOXICOLOGY Presenter: • Dr. Jasmine Drake, Graduate Program Director and Assistant Professor, Administration of Justice Department, Barbara Jordan-Mickey Leland School of Public Affairs, Texas Southern University NACDL Training Defending Drug Overdose Homicides in Pennsylvania Penn State Harrisburg, Middletown, PA November 6th, 2019 11:30- 12:45 p.m. Understanding & Challenging the Drugs: Chemistry & Toxicology Dr. Jasmine Drake, Forensic Science Learning Laboratory, Texas Southern University I. Opioid Drug Classifications A. Types of Opioids B. Classic vs. Synthetic C. Toxicology of Opioids 1) How opioids interact with the body 2) Addiction (psychological vs. physiological II. New Classes of Drugs A. Emerging Threats B. Potency III. National Trends in Opioid Overdose Deaths in the U.S. A. Based on State B. Ethnicity C. Drug-Type (prescription vs. fentanyl vs. heroin) IV. Trends of Opioid Overdose Deaths in Philadelphia A. Based on Ethnicity B. Drug Type (prescription vs. fentanyl vs. heroin) V. Legal Considerations to the Opioid Epidemic A. Punitive Measures vs. Rehabilitative Treatment B. Progressive Jurisdictions Nationwide C. New Legal Measures in Philadelphia VI. Toxicology Reports A. What’s in the report? B. Key Aspects of the Tox Report C. Terminology D. Evaluating and Interpreting the data? E. Questions and considerations. VII. Conclusion and Discussion A. Case Specific Examples B. Sample Toxicology Reports The Opioid Epidemic: What labs have to do with it? Ewa King, Ph.D. Associate Director of Health RIDOH State Health Laboratories Analysis. Answers. Action. www.aphl.org Overview • Overdose trends • Opioids and their effects • Analytical testing approaches • Toxicology laboratories Analysis. Answers. Action. -
WHO Expert Committee on Drug Dependence
WHO Technical Report Series 1034 This report presents the recommendations of the forty-third Expert Committee on Drug Dependence (ECDD). The ECDD is responsible for the assessment of psychoactive substances for possible scheduling under the International Drug Control Conventions. The ECDD reviews the therapeutic usefulness, the liability for abuse and dependence, and the public health and social harm of each substance. The ECDD advises the Director-General of WHO to reschedule or to amend the scheduling status of a substance. The Director-General will, as appropriate, communicate the recommendations to the Secretary-General of the United Nations, who will in turn communicate the advice to the Commission on Narcotic Drugs. This report summarizes the findings of the forty-third meeting at which the Committee reviewed 11 psychoactive substances: – 5-Methoxy-N,N-diallyltryptamine (5-MeO-DALT) WHO Expert Committee – 3-Fluorophenmetrazine (3-FPM) – 3-Methoxyphencyclidine (3-MeO-PCP) on Drug Dependence – Diphenidine – 2-Methoxydiphenidine (2-MeO-DIPHENIDINE) Forty-third report – Isotonitazene – MDMB-4en-PINACA – CUMYL-PEGACLONE – Flubromazolam – Clonazolam – Diclazepam The report also contains the critical review documents that informed recommendations made by the ECDD regarding international control of those substances. The World Health Organization was established in 1948 as a specialized agency of the United Nations serving as the directing and coordinating authority for international health matters and public health. One of WHO’s constitutional functions is to provide objective, reliable information and advice in the field of human health, a responsibility that it fulfils in part through its extensive programme of publications. The Organization seeks through its publications to support national health strategies and address the most pressing public health concerns of populations around the world. -
Measures and CDS for Safer Opioid Prescribing: a Literature Review
Measures and CDS for Safer Opioid Prescribing: A Literature Review Measures and CDS for Safer Opioid Prescribing: A Literature Review Executive Summary The U.S. opioid epidemic continues to pose significant challenges for patients, families, clinicians, and public health policy. Opioids are responsible for an estimated 315,000 deaths (from 1999 to 2016) and have caused 115 deaths per day.1 In 2017, the U.S. Department of Health and Human Services declared the opioid epidemic a public health crisis.2 The total economic burden of opioid abuse in the United States has been estimated to be $78.5 billion per year.3 Although providing care for chronic opioid users is important, equally vital are efforts to prevent so-called opioid-naïve patients (patients with no history of opioid use) from developing regular opioid use, misuse, or abuse. However, much remains unclear regarding what role clinician prescribing habits play and what duration or dose of opioids may safely be prescribed without promoting long-term use.4,5 In 2013, ECRI Institute convened the Partnership for Health IT Patient Safety, and its component, single-topic-focused workgroups followed. For this subject, the Electronic Health Record Association (EHRA): Measures and Clinical Decision Support (CDS) for Safer Opioid Prescribing workgroup included members from the Healthcare Information and Management Systems Society (HIMSS) EHRA and the Partnership team. The project was oriented towards exploring methods to enable a synergistic cycle of performance measurement and identifying electronic health record (EHR)/health information technology (IT)–enabled approaches to support healthcare organizations’ ability to assess and measure opioid prescribing. -
Accurate Prediction of Terahertz Spectra of Molecular Crystals of Fentanyl and Its Analogs Chun‑Hung Wang1, Anthony C
www.nature.com/scientificreports OPEN Accurate prediction of terahertz spectra of molecular crystals of fentanyl and its analogs Chun‑Hung Wang1, Anthony C. Terracciano2,3, Artёm E. Masunov1,4,5*, Mengyu Xu3,6 & Subith S. Vasu2,3 Fentanyl is a potent synthetic opioid pain reliever with a high bioavailability that can be used as prescription anesthetic. Rapid identifcation via non‑contact methods of both known and emerging opioid substances in the fentanyl family help identify the substances and enable rapid medical attention. We apply PBEh‑3c method to identify vibrational normal modes from 0.01 to 3 THz in solid fentanyl and its selected analogs. The molecular structure of each fentanyl analog and unique arrangement of H‑bonds and dispersion interactions signifcantly change crystal packing and is subsequently refected in the THz spectrum. Further, the study of THz spectra of a series of stereoisomers shows that small changes in molecular structure results in distinct crystal packing and signifcantly alters THz spectra as well. We discuss spectral features of synthetic opioids with higher potency than conventional fentanyl such as ohmefentanyl and sufentanil and discover the pattern of THz spectra of fentanyl analogs. Fentanyl (N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]propionanilide)1 is one kind of synthetic opioid used for pain relief, which has high afnity for μ-opioid receptor and acts as an agonist with higher potency than 2,3 morphine. Its efective dose (ED 95) is 0.45–0.60 μg/kg, partly due to its 92% bioavailability . A comprehensive review of the history of fentanyl and its analogs has been published in 2018 by Armenian et al.4 Carfentanil5, sufentanil6, alfentanil7, and remifentanil8 are fentanyl analogs with additional functional groups which enable a higher potency than fentanyl itself. -
Values of Several Opioid Receptor Agonists and Their Liability to Cause Depen- Dence
Acta Pharmacologica Sinica (2010) 31: 393–398 npg © 2010 CPS and SIMM All rights reserved 1671-4083/10 $32.00 www.nature.com/aps Original Article Paradoxical relationship between RAVE (relative activity versus endocytosis) values of several opioid receptor agonists and their liability to cause depen- dence Yu-hua WANG1, 2, 3, Jian-feng SUN3, Yi-min TAO3, Xue-jun XU3, Zhi-qiang CHI3, Jing-gen LIU3, * 1School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China; 2School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China; 3State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China Aim: To examine the relationship between the RAVE (relative activity versus endocytosis) values of opiate agonists and their dependence liability by studying several potent analgesics with special profiles in the development of physical and psychological dependence. Methods: The effects of (–)-cis-(3R,4S,2′R) ohmefentanyl (F9202), (+)-cis-(3R,4S,2′S) ohmefentanyl (F9204), dihydroetorphine (DHE) and morphine on [35S]GTPγS binding, forskolin-stimulated cAMP accumulation, and receptor internalization were studied in CHO cells stably expressing HA-tagged μ-opioid receptors (CHO-HA-MOR). cAMP overshoot in response to the withdrawal of these compound treatments was also tested. Results: All four agonists exhibited the same rank order of activity in stimulation of [35S]GTPγS binding, inhibition of adenylyl cyclase (AC) and induction of receptor internalization: DHE>F9204>F9202>morphine. Based on these findings and the previous in vivo analgesic data obtained from our and other laboratories, the RAVE values of the four agonists were calculated. -
Critical Review Report: CROTONYLFENTANYL
Critical Review Report: CROTONYLFENTANYL Expert Committee on Drug Dependence Forty-second Meeting Geneva, 21-25 October 2019 This report contains the views of an international group of experts, and does not necessarily represent the decisions or the stated policy of the World Health Organization 42nd ECDD (2019): Crotonylfentanyl © World Health Organization 2019 All rights reserved. nd This is an advance copy distributed to the participants of the 42 Expert Committee on Drug Dependence, before it has been formally published by the World Health Organization. The document may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in any form or by any means without the permission of the World Health Organization. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. The World Health Organization does not warrant that the information contained in this publication is complete and correct and shall not be liable for any damages incurred as a result of its use.