DOCSLIB.ORG

Deltorphin Transport Across the Blood–Brain Barrier

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Deltorphin Transport Across the Blood–Brain Barrier Proc. Natl. Acad. Sci. USA Vol. 94, pp. 9469–9474, August 1997 Pharmacology Deltorphin transport across the blood–brain barrier ANNA FIORI*†,PATRIZIA CARDELLI‡,LUCIA NEGRI§,MARIA ROSARIA SAVI*, ROBERTO STROM‡, AND VITTORIO ERSPAMER§ *Department of Biochemical Sciences ‘‘A. Rossi Fanelli’’, ‡Department of Cellular Biotechnology and Hematology, and §Institute of Medical Pharmacology, University ‘‘La Sapienza’’, 00185 Rome, Italy Contributed by Vittorio Erspamer, June 30, 1997 ABSTRACT In vivo antinociception studies demonstrate PTS-1, -2, -3, and -4, could accelerate the entrance of opioids that deltorphins are opioid peptides with an unusually high and related peptides into the brain. More recently, the use of blood–brain barrier penetration rate. In vitro, isolated bovine different in vitro models consisting either of fresh isolated brain microvessels can take up deltorphins through a satu- brain microvessels or of cultured brain endothelial cells has rable nonconcentrative permeation system, which is appar- allowed a better investigation of the modality of transport of ently distinct from previously described systems involved in some opioid peptides such as Met-enkephalin and related the transport of neutral amino acids or of enkephalins. analogs (25–27). Deltorphins are naturally occurring peptides Removing Na1 ions from the incubation medium decreases with high affinity and selectivity for d-opioid receptors. These the carrier affinity for deltorphins (225%), but does not affect opioids have a D-amino acid residue in position 2 of their the Vmax value of the transport. The nonselective opiate sequence and an amide residue at C terminus that protect them antagonist naloxone inhibits deltorphin uptake by brain mi- from enzymatic hydrolysis (28). In this study, we show that, crovessels, but neither the selective d-opioid antagonist nal- when injected intravenously in mice, deltorphins enter BBB to trindole nor a number of opioid peptides with different produce antinociception. Moreover, using isolated bovine affinities for d-orm-opioid receptors compete with deltor- brain microvessels as an in vitro model of the BBB, we phins for the transport. Binding studies demonstrate that m-, investigate the presence of transport system(s) for deltorphins d-, and k-opioid receptors are undetectable in the microvessel in the plasma membranes of the endothelial cells and whether preparation. Preloading of the microvessels with L-glutamine and how such system(s) are susceptible to regulation, in results in a transient stimulation of deltorphin uptake. Glu- particular at the metabolic level. tamine-accelerated deltorphin uptake correlates to the rate of glutamine efflux from the microvessels and is abolished by MATERIALS AND METHODS naloxone. Chemicals. Tyr-ala-Phe-Asp-Val-Val-Gly-NH2 (deltorphin The blood–brain barrier (BBB) accounts for the restricted I; ala, D-Ala), Tyr-ala-Phe-Glu-Val-Val-Gly-NH2 (deltorphin movement of solutes between the vascular and the cerebral II), and Tyr-ala-Gly-NMePhe-glycinol (DAMGO) were ob- compartments. Its anatomical counterpart has been identified tained from Bachem. Tyr-D-Pen-Gly-Phe-D-Pen (DPEDPE), as the endothelial cell membranes of brain microvessels (1–5). Tyr-ala-Phe-Gly-Tyr-Pro-Ser-NH2 (dermorphin), Tyr-Gly- These endothelial cells, joined together by tight junctions (6), Gly-Phe-Leu-OH (Leu-enkephalin), Tyr-Gly-Gly-Phe- form a continuous physical barrier playing a crucial role in Met-OH (Met-enkephalin), Hepes, naloxone, and naltrindole determining the rate at which different compounds can reach, were from Sigma); morphine HCl was from Salars (Como, or in turn leave, the central nervous system (CNS). The Italy); carboxyfluorescein diacetate was from Molecular capacity of any particular molecule to penetrate the BBB Probes. [Lys7]dermorphin was synthesized as indicated by depends essentially on its free diffusion across the cell walls— Negri and coworkers (28). All other chemicals were obtained i.e., on its lipid solubility—or on its specific affinity for a from Merck or Fluka. [Tyrosyl-3,5-3H]Leu-enkephalin (37 carrier-mediated transport system. The use of isolated brain Ciymmol; 1 Ci 5 37 GBq), [tyrosyl-3,5-3H]deltorphin I (35 microvessels, as an in vitro model of the BBB, has allowed the Ciymmol), [tyrosyl-3,5-3H]deltorphin II (54.5 Ciymmol), [ty- identification and characterization of some peculiarities of the rosyl-3,5-3H]DAMGO (37 Ciymmol), [phenyl-3,4-3H]U-69593 transport systems specific for sugars (7, 8), amino acids (9–13), {(1)-(5a,7a,8b)-N-methyl-N[7-(1-pyrrolidinyl)-1-oxaspiro- electrolytes (14, 15), or transferrin (16). It had been initially (4,5)dec-8-yl]-benzeneacetamide} (47 Ciymmol), L-[3,4- assumed that peptides could not enter the CNS via the BBB 3H(N)]glutamine (60 Ciymmol), L-[U-14C]leucine (300 mCiy (17) and that the entry rate into the CNS of some peptides mmol), L-[U-14C]tyrosine (450 mCiymmol), [U-14C]sucrose correlated only with their lipid solubility, suggesting that they (4.63 mCiymmol), and Aquasol-2 were obtained from New crossed the BBB by direct diffusion through the phospholipid England Nuclear. bilayer of the endothelial cell membranes. It is now generally Intracerebroventricular (i.c.v.) and Intravenous (i.v.) In- accepted, instead, that different categories of peptides can jections. Male C57BL6 mice weighing 25–28 g (Charles River enter or exit the CNS through the endothelial cell membranes Breeding Laboratories) were housed singly in 20 3 25 cm cages of brain microvessels at a rate higher than that accounted by placed in a thermostatically controlled cabinet at an environ- passive diffusion. In vivo studies have indicated the existence mental temperature of 21°C. Under light diethyl ether anes- of transport systems that allow the selective permeation of the thesia drug solution or vehicle were delivered into the lateral BBB by different peptides, either endogenous or synthetic cerebral ventricle (i.c.v.) by using a modification of the method (18–24). Some years ago, Banks and Kastin (21) have sug- of Haley and McCormick (29). An incision was made in the gested that at least four different transport systems, named Abbreviations: ala, D-Ala; BBB, blood-brain barrier; BBB-PI, BBB The publication costs of this article were defrayed in part by page charge permeability index; DAMGO, Tyr-ala-Gly-NMePhe-glycinol; DPEDPE, Tyr-D-Pen-Gly-Phe-D-Pen; i.c.v., intracerebroventricular; payment. This article must therefore be hereby marked ‘‘advertisement’’ in i.v., intravenous; U-69593, (1)-(5a,7a,8b)-N-methyl-N[7-(1- accordance with 18 U.S.C. §1734 solely to indicate this fact. pyrrolidinyl)-1-oxaspiro(4,5)dec-8-yl]-benzeneacetamide. © 1997 by The National Academy of Sciences 0027-8424y97y949469-6$2.00y0 *To whom reprint requests should be addressed. e-mail: strom@ PNAS is available online at http:yywww.pnas.org. dbu.roma1.it. 9469 Downloaded by guest on October 4, 2021 9470 Pharmacology: Fiori et al. Proc. Natl. Acad. Sci. USA 94 (1997) scalp and the bregma was located. Injections were made Table 1. BBB-PI of deltorphins compared to morphine and other directly through the skull at a point 2 mm caudal and 2 mm opioid peptides lateral to bregma at a depth of 3 mm using a Hamilton i.v. ED50, i.c.v. ED50, BBB-PI microliter syringe with a 26-gauge needle. All i.c.v. injections Compound nmol nmol 3 1024 were made in a volume of 5 ml. For i.v. injections the mouse tail was immersed in moderately hot water (about 40°C) for Deltorphin I 321.0 0.38 12 1–2 min to induce venous dilatation and the injections carried Deltorphin II 364.0 0.27 9 out using a 500 ml Hamilton syringe with a 25-gauge needle. DAMGO 315.0 0.04 1 Test of Antinociception. Antinociception responses were Dermorphin 64.0 0.03 3 7 determined by immerging the mouse tail into hot water (55°C). [Lys ]dermorphin 7.4 0.04 28 The latency of the first sign of a rapid tail-flick was taken as Morphine 130.0 18.13 1980 the end point, as indicated by Janssen et al. (30). Before drug For calculation of BB-PI, see text. administration, mice not flicking their tails within 5 sec from hot water immersion were eliminated from the study. After in triplicate by omitting the microvessels, was constantly below drug injection, animals not flicking their tails within 15 sec 100 dpm. were removed from the nociceptive stimulus and assigned a By plotting the initial rate of uptake, v°, as a function of maximal antinociceptive response. The test was repeated every peptide concentration, a typical saturation kinetics pattern was 15 min after i.c.v. or i.v. drug injection and time course found, often superimposed to a diffusional component that antinociception curves were drawn. Peak response (PR), area could, however, be easily subtracted (11, 33). Nonlinear re- under the curve (AUC), and PRyAUC ratios were calculated gression analysis, performed on the v° vs. v°y[S] ‘‘Eadie– for the dose producing 50% of the maximum response (ED50). Hofstee plot,’’ which allows the use of simple statistical Five mice were tested for each opioid dose. procedures (34), was used to obtain the optimal estimates of BBB Permeability Index. The values of i.v. and i.c.v. ED50 the kinetic parameters of the transport system(s) and to were multiplied by the respective PRyAUC ratio to normalize evaluate the standard error impending on them. Because them for degradation and elimination processes, and the BBB labeled sucrose had been shown not to permeate the endo- permeability index (BBB-PI) was calculated as the ratio be- thelial cells (9), the intracellular water space could be evalu- tween i.c.v.yi.v. normalized ED50 values.
Load more

Recommended publications
  • 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.
    [Show full text]
  • INVESTIGATION of NATURAL PRODUCT SCAFFOLDS for the DEVELOPMENT of OPIOID RECEPTOR LIGANDS by Katherine M
    INVESTIGATION OF NATURAL PRODUCT SCAFFOLDS FOR THE DEVELOPMENT OF OPIOID RECEPTOR LIGANDS By Katherine M. Prevatt-Smith Submitted to the graduate degree program in Medicinal Chemistry and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. _________________________________ Chairperson: Dr. Thomas E. Prisinzano _________________________________ Dr. Brian S. J. Blagg _________________________________ Dr. Michael F. Rafferty _________________________________ Dr. Paul R. Hanson _________________________________ Dr. Susan M. Lunte Date Defended: July 18, 2012 The Dissertation Committee for Katherine M. Prevatt-Smith certifies that this is the approved version of the following dissertation: INVESTIGATION OF NATURAL PRODUCT SCAFFOLDS FOR THE DEVELOPMENT OF OPIOID RECEPTOR LIGANDS _________________________________ Chairperson: Dr. Thomas E. Prisinzano Date approved: July 18, 2012 ii ABSTRACT Kappa opioid (KOP) receptors have been suggested as an alternative target to the mu opioid (MOP) receptor for the treatment of pain because KOP activation is associated with fewer negative side-effects (respiratory depression, constipation, tolerance, and dependence). The KOP receptor has also been implicated in several abuse-related effects in the central nervous system (CNS). KOP ligands have been investigated as pharmacotherapies for drug abuse; KOP agonists have been shown to modulate dopamine concentrations in the CNS as well as attenuate the self-administration of cocaine in a variety of species, and KOP antagonists have potential in the treatment of relapse. One drawback of current opioid ligand investigation is that many compounds are based on the morphine scaffold and thus have similar properties, both positive and negative, to the parent molecule. Thus there is increasing need to discover new chemical scaffolds with opioid receptor activity.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • Intravta Deltorphin, but Not DPDPE, Induces Place Preference in Ethanoldrinking Rats
    ALCOHOLISM:CLINICAL AND EXPERIMENTAL RESEARCH Vol. 38, No. 1 January 2014 Intra-VTA Deltorphin, But Not DPDPE, Induces Place Preference in Ethanol-Drinking Rats: Distinct DOR-1 and DOR-2 Mechanisms Control Ethanol Consumption and Reward Jennifer M. Mitchell, Elyssa B. Margolis, Allison R. Coker, Daicia C. Allen, and Howard L. Fields Background: While there is a growing body of evidence that the delta opioid receptor (DOR) modu- lates ethanol (EtOH) consumption, development of DOR-based medications is limited in part because there are 2 pharmacologically distinct DOR subtypes (DOR-1 and DOR-2) that can have opposing actions on behavior. Methods: We studied the behavioral influence of the DOR-1-selective agonist [D-Pen2,D-Pen5]- Enkephalin (DPDPE) and the DOR-2-selective agonist deltorphin microinjected into the ventral tegmental area (VTA) on EtOH consumption and conditioned place preference (CPP) and the physio- logical effects of these 2 DOR agonists on GABAergic synaptic transmission in VTA-containing brain slices from Lewis rats. Results: Neither deltorphin nor DPDPE induced a significant place preference in EtOH-na€ıve Lewis rats. However, deltorphin (but not DPDPE) induced a significant CPP in EtOH-drinking rats. In con- trast to the previous finding that intra-VTA DOR-1 activity inhibits EtOH consumption and that this inhibition correlates with a DPDPE-induced inhibition of GABA release, here we found no effect of DOR-2 activity on EtOH consumption nor was there a correlation between level of drinking and deltorphin-induced change in GABAergic synaptic transmission. Conclusions: These data indicate that the therapeutic potential of DOR agonists for alcohol abuse is through a selective action at the DOR-1 form of the receptor.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • Receptor Types
    Proc. Natl. Acad. Sci. USA Vol. 87, pp. 3180-3184, April 1990 Pharmacology Chimeric opioid peptides: Tools for identifying opioid receptor types (dynorphin/dermorphin/deltorphin/monoclonal antibody/panning) Guo-xi XIE*t, ATSUSHI MIYAJIMA*, TAKASHI YOKOTA*, KEN-ICHI ARAI*, AND AVRAM GOLDSTEINt *Department of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304; and tDepartment of Pharmacology, Stanford University, Stanford, CA 94305 Contributed by Avram Goldstein, January 23, 1990 ABSTRACT We synthesized several chimeric peptides in was assumed that the C-terminal amide group ofdermorphin, which the N-terminal nine residues of dynorphin-32, a peptide deltorphins, and DSLET and the alcohol group of DAGO selective for the K opioid receptor, were replaced by opioid could be removed without affecting opioid binding. By anal- peptides selective for other opioid receptor types. Each chi- ogy to dyn-32, which binds selectively to K opioid sites, meric peptide retained the high affminty and type selectivity DAGO-DYN and dermorphin-DYN should bind selectively characteristic of its N-terminal sequence. The common C- to p.; deltorphins-DYN and DSLET-DYN should bind selec- terminal two-thirds of the chimeric peptides served as an tively to 8. mAbs 17.M and 39 should act as nonblocking epitope recognized by the same monoclonal antibody. When antibodies to all these peptides. bound to receptors on a cell surface or membrane preparation, In the present study, we have demonstrated that the these peptides could still bind specifically to the monoclonal chimeric peptides do maintain the high affinities and type antibody. These chimeric peptides should be useful for isolating selectivities of their N-terminal sequences.
    [Show full text]
  • 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
    [Show full text]
  • Download an Information Sheet on Opiate Use During Pregnancy
    PARENT/FAMILY EDUCATION OPIATE USE DURING PREGNANCY childrensMN.org OPIATES Medications or drugs known as opiates (or narcotics) are commonly prescribed OPIATE USE DURING for pain. The most common names of these drugs include OxyContin, Percocet, PREGNANCY: HOW DOES IT Vicodin, morphine and methadone. Use of opiates during pregnancy often causes AFFECT MOTHERS AND BABIES? complications for mothers as well as complications for babies exposed to opiates in the womb. Illegal opiates like heroin also cause risks for mother and baby. During pregnancy, everything you eat or drink can have an effect on Prescription opiates can be used illegally, or taken at higher doses than prescribed. your unborn baby. This includes Use of any form of opiate can lead to dependency which has been observed medications, drugs, alcohol and in the rapidly increasing number of young women that have developed opiate tobacco. Certain substances are dependency in the past 10 years. Many people who have become dependent on not safe during pregnancy and you prescription opiates are also at risk of using heroin. should review any medications, drugs (over the counter, prescribed The newborn baby exposed to opiates in the womb may have withdrawal and illegal), supplements, or herbs symptoms after being born. When babies have symptoms of withdrawal, they often that you are taking with your need to stay in the hospital longer and may not be able to stay in their mother’s doctor or midwife. By informing room. Instead, they may need the close observation and care that is given in a your care team about ALL drugs special care nursery.
    [Show full text]