Heterodimerization of Μ and Δ Opioid Receptors: a Role in Opiate Synergy
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The in Vitro Binding Properties of Non-Peptide AT1 Receptor Antagonists
Journal of Clinical and Basic Cardiology An Independent International Scientific Journal Journal of Clinical and Basic Cardiology 2002; 5 (1), 75-82 The In Vitro Binding Properties of Non-Peptide AT1 Receptor Antagonists Vanderheyden PML, Fierens FLP, Vauquelin G, Verheijen I Homepage: www.kup.at/jcbc Online Data Base Search for Authors and Keywords Indexed in Chemical Abstracts EMBASE/Excerpta Medica Krause & Pachernegg GmbH · VERLAG für MEDIZIN und WIRTSCHAFT · A-3003 Gablitz/Austria REVIEWS Binding of Non-Peptide AT1 Receptor Antagonists J Clin Basic Cardiol 2002; 5: 75 The In Vitro Binding Properties of Non-Peptide AT1 Receptor Antagonists P. M. L. Vanderheyden, I. Verheijen, F. L. P. Fierens, G. Vauquelin A major breakthrough in the development of AT1 receptor antagonists as promising antihypertensive drugs, was the synthe- sis of potent and selective non-peptide antagonists for this receptor. In the present manuscript an overview of the in vitro binding properties of these antagonists is discussed. In particular, CHO cells expressing human AT1 receptors offer a well- defined and efficient experimental system, in which antagonist binding and inhibition of angiotensin II induced responses could be measured. From these studies it appeared that all investigated antagonists were competitive with respect to angiotensin II and bind to a common or overlapping binding site on the receptor. Moreover this model allowed us to describe the mecha- nism by which certain antagonists depress the maximal angiotensin II responsiveness in vascular contraction studies. Insur- mountable inhibition was found to be related to the dissociation rate of the antagonist-AT1 receptor complex. The almost complete (candesartan), partially insurmountable inhibition (irbesartan, EXP3174, valsartan) or surmountable inhibition (losartan), was explained by the ability of the antagonist-receptor complex to adopt a fast and slow reversible state. -
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. -
Medications to Treat Opioid Use Disorder Research Report
Research Report Revised Junio 2018 Medications to Treat Opioid Use Disorder Research Report Table of Contents Medications to Treat Opioid Use Disorder Research Report Overview How do medications to treat opioid use disorder work? How effective are medications to treat opioid use disorder? What are misconceptions about maintenance treatment? What is the treatment need versus the diversion risk for opioid use disorder treatment? What is the impact of medication for opioid use disorder treatment on HIV/HCV outcomes? How is opioid use disorder treated in the criminal justice system? Is medication to treat opioid use disorder available in the military? What treatment is available for pregnant mothers and their babies? How much does opioid treatment cost? Is naloxone accessible? References Page 1 Medications to Treat Opioid Use Disorder Research Report Discusses effective medications used to treat opioid use disorders: methadone, buprenorphine, and naltrexone. Overview An estimated 1.4 million people in the United States had a substance use disorder related to prescription opioids in 2019.1 However, only a fraction of people with prescription opioid use disorders receive tailored treatment (22 percent in 2019).1 Overdose deaths involving prescription opioids more than quadrupled from 1999 through 2016 followed by significant declines reported in both 2018 and 2019.2,3 Besides overdose, consequences of the opioid crisis include a rising incidence of infants born dependent on opioids because their mothers used these substances during pregnancy4,5 and increased spread of infectious diseases, including HIV and hepatitis C (HCV), as was seen in 2015 in southern Indiana.6 Effective prevention and treatment strategies exist for opioid misuse and use disorder but are highly underutilized across the United States. -
A,-, and P-Opioid Receptor Agonists on Excitatory Transmission in Lamina II Neurons of Adult Rat Spinal Cord
The Journal of Neuroscience, August 1994, 74(E): 4965-4971 Inhibitory Actions of S,-, a,-, and p-Opioid Receptor Agonists on Excitatory Transmission in Lamina II Neurons of Adult Rat Spinal Cord Steven R. Glaum,’ Richard J. Miller,’ and Donna L. Hammond* Departments of lPharmacoloaical and Phvsioloqical Sciences and ‘Anesthesia and Critical Care, The University of Chicago, Chicago, Illinois 60637 . This study examined the electrophysiological consequences tor in rat spinal cord and indicate that activation of either of selective activation of 6,-, 6,-, or r-opioid receptors using 6,- or Qopioid receptors inhibits excitatory, glutamatergic whole-cell recordings made from visually identified lamina afferent transmission in the spinal cord. This effect may me- II neurons in thin transverse slices of young adult rat lumbar diate the ability of 6, or 6, receptor agonists to produce an- spinal cord. Excitatory postsynaptic currents (EPSCs) or po- tinociception when administered intrathecally in the rat. tentials (EPSPs) were evoked electrically at the ipsilateral [Key words: DPDPE, deltorphin, spinal cord slice, EPSP, dorsal root entry zone after blocking inhibitory inputs with 6-opioid receptor, DAMGO, naltriben, 7-benzylidene- bicuculline and strychnine, and NMDA receptors with o-2- naltrexone (BNTX), naloxone] amino+phosphonopentanoic acid. Bath application of the p receptor agonist [D-Ala2, KMePhe4, Gly5-ollenkephalin (DAMGO) or the 6, receptor agonist [D-Pen2, o-PerF]en- The dorsal horn of the spinal cord is an important site for the kephalin (DPDPE) produced a log-linear, concentration-de- production of antinociception by K- and 6-opioid receptor ag- pendent reduction in the amplitude of the evoked EPSP/ onists (Yaksh, 1993). -
The Opioid Epidemic: What Labs Have to Do with It?
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. www.aphl.org Opioid overdose crisis 1 Analysis. Answers. Action. www.aphl.org Opioid overdose crisis 2 Analysis. Answers. Action. www.aphl.org Opiates and Opioids • Opiates vs. Opioids • Opiates: Naturally occurring, derived from the poppy plant • Opioids: “Opiate-like” drugs in effects, not chemical structure Includes opiates • Narcotic analgesics • CNS depressants • DEA Schedule I or II controlled substances • Additive effect with other CNS depressant drugs Analysis. Answers. Action. www.aphl.org Efficacy of Opioids • How do opioids work? • Bind with opioid receptors • Brain, spinal cord, GI tract, and throughout the body • Pain, emotion, breathing, movement, and digestion Opioid Receptor Analysis. Answers. Action. www.aphl.org Effects of Opioids Physiological Psychological • Pain relief • Drowsiness/ sedation • Cough suppression • Mental confusion • GI motility • Loss of memory • Respiratory depression • Lethargy/ apathy • Pupillary constriction • Euphoria/ tranquility • Itching • Mood swings • Constipation • Depression • Dependence • Withdrawal • Dependence Analysis. Answers. Action. www.aphl.org Opiates 1 Opiates • Naturally occurring alkaloids Opium • Latex from the opium poppy plant Codeine: • Mild to moderate pain • Antitussive Morphine: • Severe pain • Metabolite of codeine and heroin Analysis. Answers. Action. www.aphl.org Opiates 2 Semi-synthetic Opiates: • Synthesized from a natural opiate Heroin: • Schedule I narcotic Hydrocodone (Vicodin): • Mild to moderate pain • Metabolizes to hydromorphone (Dilaudid) Oxycodone (Oxycontin/Percocet): • Moderate to severe pain • Metabolizes to oxymorphone (Opana) Analysis. Answers. Action. -
1 Title Page Pharmacological Comparison of Mitragynine and 7
JPET Fast Forward. Published on December 31, 2020 as DOI: 10.1124/jpet.120.000189 This article has not been copyedited and formatted. The final version may differ from this version. JPET-AR-2020-000189R1: Obeng et al. Pharmacological Comparison of Mitragynine and 7-Hydroxymitragynine: In Vitro Affinity and Efficacy for Mu-Opioid Receptor and Morphine-Like Discriminative-Stimulus Effects in Rats. Title Page Pharmacological Comparison of Mitragynine and 7-Hydroxymitragynine: In Vitro Affinity and Efficacy for Mu-Opioid Receptor and Opioid-Like Behavioral Effects in Rats Samuel Obeng1,2,#, Jenny L. Wilkerson1,#, Francisco León2, Morgan E. Reeves1, Luis F. Restrepo1, Lea R. Gamez-Jimenez1, Avi Patel1, Anna E. Pennington1, Victoria A. Taylor1, Nicholas P. Ho1, Tobias Braun1, John D. Fortner2, Morgan L. Crowley2, Morgan R. Williamson1, Victoria L.C. Pallares1, Marco Mottinelli2, Carolina Lopera-Londoño2, Christopher R. McCurdy2, Lance R. McMahon1, and Takato Hiranita1* Downloaded from Departments of Pharmacodynamics1 and Medicinal Chemistry2, College of Pharmacy, University of Florida jpet.aspetjournals.org #These authors contributed equally Recommended section: Behavioral Pharmacology at ASPET Journals on September 29, 2021 Correspondence: *Takato Hiranita, Ph.D. Department of Pharmacodynamics, College of Pharmacy, University of Florida 1345 Center Drive, Gainesville, FL 32610 Email: [email protected] Phone: +1.352.294.5411 Fax: +1.352.273.7705 Keywords: kratom, mitragynine, 7-hydroxymitragynine, morphine, opioid, discriminative stimulus Conflicts of Interests or Disclaimers: None Manuscript statistics: Number of text pages: 56 Number of tables: 7 Number of figures: 10 Number of supplementary Tables: 4 Number of supplementary figures: 7 1 JPET Fast Forward. Published on December 31, 2020 as DOI: 10.1124/jpet.120.000189 This article has not been copyedited and formatted. -
Atrazine and Cell Death Symbol Synonym(S)
Supplementary Table S1: Atrazine and Cell Death Symbol Synonym(s) Entrez Gene Name Location Family AR AIS, Andr, androgen receptor androgen receptor Nucleus ligand- dependent nuclear receptor atrazine 1,3,5-triazine-2,4-diamine Other chemical toxicant beta-estradiol (8R,9S,13S,14S,17S)-13-methyl- Other chemical - 6,7,8,9,11,12,14,15,16,17- endogenous decahydrocyclopenta[a]phenanthrene- mammalian 3,17-diol CGB (includes beta HCG5, CGB3, CGB5, CGB7, chorionic gonadotropin, beta Extracellular other others) CGB8, chorionic gonadotropin polypeptide Space CLEC11A AW457320, C-type lectin domain C-type lectin domain family 11, Extracellular growth factor family 11, member A, STEM CELL member A Space GROWTH FACTOR CYP11A1 CHOLESTEROL SIDE-CHAIN cytochrome P450, family 11, Cytoplasm enzyme CLEAVAGE ENZYME subfamily A, polypeptide 1 CYP19A1 Ar, ArKO, ARO, ARO1, Aromatase cytochrome P450, family 19, Cytoplasm enzyme subfamily A, polypeptide 1 ESR1 AA420328, Alpha estrogen receptor,(α) estrogen receptor 1 Nucleus ligand- dependent nuclear receptor estrogen C18 steroids, oestrogen Other chemical drug estrogen receptor ER, ESR, ESR1/2, esr1/esr2 Nucleus group estrone (8R,9S,13S,14S)-3-hydroxy-13-methyl- Other chemical - 7,8,9,11,12,14,15,16-octahydro-6H- endogenous cyclopenta[a]phenanthren-17-one mammalian G6PD BOS 25472, G28A, G6PD1, G6PDX, glucose-6-phosphate Cytoplasm enzyme Glucose-6-P Dehydrogenase dehydrogenase GATA4 ASD2, GATA binding protein 4, GATA binding protein 4 Nucleus transcription TACHD, TOF, VSD1 regulator GHRHR growth hormone releasing -
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. -
Opiate/ Heroin Working Group Final Report
OPIATE/ HEROIN WORKING GROUP FINAL REPORT United States Attorney’s Offices For the Southern and Northern Districts of Mississippi February 28. 2017 HEROIN/OPIATE WORKING GROUP FINAL REPORT Law Enforcement and Data Group Recommendation No. 1: Implement a comprehensive data collection and dissemination program Recommendation No. 2: Heroin (Opiate) Involved Death Investigation Task Force Recommendation No. 3: Greater distribution and training on use of Naloxone Recommendation No. 4: Mandate greater reporting of overdoses and naloxone administration Recommendation No. 5: Expand and advertise availability of the dropbox program Medical Issues Group Recommendation No. 1: Adopt CDC Guidelines Recommendation No. 2: Continuing Medical Education Recommendation No. 3: Upgrades to the Prescription Monitoring Program Recommendation No. 4: Addiction Treatment Education Recommendation No. 5: Review Funding Issues for Alternative Treatments Recommendation No. 6: Limitations on Prescriptions Recommendation No. 7: Mandate increased use of PMP Recommendation No. 8: Change the definition of Pain Management Clinic Recommendation No. 9: IDs for Controlled Substance Prescriptions Treatment and Overdose Prevention Group Recommendation No. 1: More Funding for Treatment Recommendation No. 2: Youth/Juvenile Detention Systems Recommendation No. 3: Expand the availability and use of Vivitrol Recommendation No. 4: Drug Courts and Rentry programs Recommendation No. 5: Public Education and Awareness HEROIN/OPIATE WORKING GROUP FINAL REPORT The United States Attorney’s Offices for the Northern and Southern Districts of Mississippi convened an Opiate/Heroin Working Group in June 2016. At the initial meeting at the Mississippi Bureau of Narcotics (“MBN”) Headquarters, representatives from the medical, pharmaceutical, mental health, law enforcement, judiciary and many other specialties attended a full day symposium to begin the discussion about a comprehensive approach to the opiate and heroin crisis in the nation and in our state. -
Constitutive Activation of G Protein-Coupled Receptors and Diseases: Insights Into Mechanisms of Activation and Therapeutics
Pharmacology & Therapeutics 120 (2008) 129–148 Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Associate editor: S. Enna Constitutive activation of G protein-coupled receptors and diseases: Insights into mechanisms of activation and therapeutics Ya-Xiong Tao ⁎ Department of Anatomy, Physiology and Pharmacology, 212 Greene Hall, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA article info abstract The existence of constitutive activity for G protein-coupled receptors (GPCRs) was first described in 1980s. In Keywords: 1991, the first naturally occurring constitutively active mutations in GPCRs that cause diseases were reported G protein-coupled receptor Disease in rhodopsin. Since then, numerous constitutively active mutations that cause human diseases were reported Constitutively active mutation in several additional receptors. More recently, loss of constitutive activity was postulated to also cause Inverse agonist diseases. Animal models expressing some of these mutants confirmed the roles of these mutations in the Mechanism of activation pathogenesis of the diseases. Detailed functional studies of these naturally occurring mutations, combined Transgenic model with homology modeling using rhodopsin crystal structure as the template, lead to important insights into the mechanism of activation in the absence of crystal structure of GPCRs in active state. Search for inverse Abbreviations: agonists on these receptors will be critical for correcting the diseases cause by activating mutations in GPCRs. ADRP, autosomal dominant retinitis pigmentosa Theoretically, these inverse agonists are better therapeutics than neutral antagonists in treating genetic AgRP, Agouti-related protein AR, adrenergic receptor diseases caused by constitutively activating mutations in GPCRs. CAM, constitutively active mutant © 2008 Elsevier Inc. -
(Oxycontin®) and Oxymorphone (Opana® ER) Reference Number: ERX.NSST.17 Effective Date: 06/15 Revision Log Last Review Date: 09/16
Clinical Policy: extended-release oxycodone (OxyContin®) and oxymorphone (Opana® ER) Reference Number: ERX.NSST.17 Effective Date: 06/15 Revision Log Last Review Date: 09/16 Clinical policies are intended to be reflective of current scientific research and clinical thinking. This policy is current at the time of approval, may be updated and therefore is subject to change. This Clinical Policy is not intended to dictate to providers how to practice medicine, nor does it constitute a contract or guarantee regarding payment or results. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. This policy is the property of Envolve Pharmacy Solutions. Unauthorized copying, use, and distribution of this Policy or any information contained herein is strictly prohibited. By accessing this policy, you agree to be bound by the foregoing terms and conditions, in addition to the Site Use Agreement for Health Plans associated with Envolve Pharmacy Solutions. Description The intent of the criteria is to ensure that patients follow selection elements established by Envolve Pharmacy Solutions for the use of extended-release oxycodone (OxyContin®) and oxymorphone (Opana® ER). Policy/Criteria It is the policy of health plans affiliated with Envolve Pharmacy Solutions® that extended-release oxycodone (OxyContin®) and oxymorphone (Opana® ER) are medically necessary for members meeting the following criteria: Initial Approval Criteria (must meet all): A. Failure of an immediate-release (short-acting) narcotic analgesic; B. Failure of fentanyl patch and morphine extended-release tablets/capsules in the past 6 months, unless intolerant or contraindicated; C. -
Drug Class Review Long-Acting Opioid Analgesics
Drug Class Review Long-Acting Opioid Analgesics 28:08.08 Opiate Agonists Transdermal Buprenorphine transdermal system (Butrans®) Fentanyl transdermal system (Duragesic®) Oral Buprenorphine oral buccal film (Belbuca®) Hydrocodone ER (Zohydro ER®, Hysingla ER®) Hydromorphone hydrochloride extended-release tablets (Exalgo®) Methadone tablets (Dolophine®) Morphine sulfate controlled-release tablets (MS Contin®, MorphaBond®) Morphine sulfate extended-release capsules (Kadian®) Oxycodone hydrochloride controlled-release tablets (OxyContin®) Oxymorphone hydrochloride extended-release (Opana ER®) Tapentadol extended-release oral tablets (Nucynta ER®) Tramadol hydrochloride extended-release capsule (Conzip, others) Tramadol hydrochloride extended-release tablet (biphasic) (Ultram ER, others) Combination Products Morphine sulfate and naltrexone extended-release capsules (Embeda®) Oxycodone ER/acetaminophen (Xartemis XR®) Final Report March 2016 Review prepared by: Vicki Frydrych, Clinical Pharmacist Melissa Archer, Clinical Pharmacist Justin Tran, PharmD Student Ryan Marcum, PharmD Student University of Utah College of Pharmacy Copyright © 2016 by University of Utah College of Pharmacy Salt Lake City, Utah. All rights reserved. Table of Contents Executive Summary ........................................................................................................................ 3 Introduction ..................................................................................................................................... 5 Table 1. Comparison