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In Vivo and in Vitro Characterization of Naltrindole-Derived
Journal of Psychopharmacology http://jop.sagepub.com/ In vivo and in vitro characterization of naltrindole-derived ligands at the κ-opioid receptor Joseph J Casal-Dominguez, Mary Clark, John R Traynor, Stephen M Husbands and Sarah J Bailey J Psychopharmacol 2013 27: 192 originally published online 31 October 2012 DOI: 10.1177/0269881112464828 The online version of this article can be found at: http://jop.sagepub.com/content/27/2/192 Published by: http://www.sagepublications.com On behalf of: British Association for Psychopharmacology Additional services and information for Journal of Psychopharmacology can be found at: Email Alerts: http://jop.sagepub.com/cgi/alerts Subscriptions: http://jop.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav >> Version of Record - Jan 23, 2013 OnlineFirst Version of Record - Oct 31, 2012 What is This? Downloaded from jop.sagepub.com at University of Bath on May 14, 2013 JOP27210.1177/0269881112464828Journal of PsychopharmacologyCasal-Dominguez et al. 4648282013 Original Paper In vivo and in vitro characterization of naltrindole-derived ligands at the κ-opioid receptor Journal of Psychopharmacology 27(2) 192 –202 © The Author(s) 2013 Reprints and permission: sagepub.co.uk/journalsPermissions.nav 1 2 2 DOI: 10.1177/0269881112464828 Joseph J Casal-Dominguez , Mary Clark , John R Traynor , jop.sagepub.com Stephen M Husbands1 and Sarah J Bailey1 Abstract Accumulating evidence supports a role for κ−opioid receptor antagonists in the treatment of mood disorders. Standard κ-antagonists have an unusual pharmacodynamic action, with a single injection blocking receptor signaling for several weeks. Here, we have characterized the κ-selective properties of two ligands, 5’-(2-aminomethyl) naltrindole (5’-AMN) and N-((Naltrindol-5-yl) methyl) pentanimidamide (5’-MABN), to identify whether modifications of the naltrindole side chain produces short-acting κ-antagonists. -
(12) United States Patent (10) Patent No.: US 9,687,445 B2 Li (45) Date of Patent: Jun
USOO9687445B2 (12) United States Patent (10) Patent No.: US 9,687,445 B2 Li (45) Date of Patent: Jun. 27, 2017 (54) ORAL FILM CONTAINING OPIATE (56) References Cited ENTERC-RELEASE BEADS U.S. PATENT DOCUMENTS (75) Inventor: Michael Hsin Chwen Li, Warren, NJ 7,871,645 B2 1/2011 Hall et al. (US) 2010/0285.130 A1* 11/2010 Sanghvi ........................ 424/484 2011 0033541 A1 2/2011 Myers et al. 2011/0195989 A1* 8, 2011 Rudnic et al. ................ 514,282 (73) Assignee: LTS Lohmann Therapie-Systeme AG, Andernach (DE) FOREIGN PATENT DOCUMENTS CN 101703,777 A 2, 2001 (*) Notice: Subject to any disclaimer, the term of this DE 10 2006 O27 796 A1 12/2007 patent is extended or adjusted under 35 WO WOOO,32255 A1 6, 2000 U.S.C. 154(b) by 338 days. WO WO O1/378O8 A1 5, 2001 WO WO 2007 144080 A2 12/2007 (21) Appl. No.: 13/445,716 (Continued) OTHER PUBLICATIONS (22) Filed: Apr. 12, 2012 Pharmaceutics, edited by Cui Fude, the fifth edition, People's Medical Publishing House, Feb. 29, 2004, pp. 156-157. (65) Prior Publication Data Primary Examiner — Bethany Barham US 2013/0273.162 A1 Oct. 17, 2013 Assistant Examiner — Barbara Frazier (74) Attorney, Agent, or Firm — ProPat, L.L.C. (51) Int. Cl. (57) ABSTRACT A6 IK 9/00 (2006.01) A control release and abuse-resistant opiate drug delivery A6 IK 47/38 (2006.01) oral wafer or edible oral film dosage to treat pain and A6 IK 47/32 (2006.01) substance abuse is provided. -
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. -
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Problems of Drug Dependence 1994: Proceedings of the 56Th Annual Scientific Meeting the College on Problems of Drug Dependence, Inc
National Institute on Drug Abuse RESEARCH MONOGRAPH SERIES Problems of Drug Dependence 1994: Proceedings of the 56th Annual Scientific Meeting The College on Problems of Drug Dependence, Inc. Volume I 152 U.S. Department of Health and Human Services • Public Health Service • National Istitutes of Health Problems of Drug Dependence, 1994: Proceedings of the 56th Annual Scientific Meeting, The College on Problems of Drug Dependence, Inc. Volume I: Plenary Session Symposia and Annual Reports Editor: Louis S. Harris, Ph.D. NIDA Research Monograph 152 1995 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 ACKNOWLEDGMENT The College on Problems of Drug Dependence, Inc., an independent, nonprofit organization, conducts drug testing and evaluations for academic institutions, government, and industry. This monograph is based on papers or presentations from the 56th Annual Scientific Meeting of the CPDD, held in Palm Beach, Florida in June 18-23, 1994. In the interest of rapid dissemination, it is published by the National Institute on Drug Abuse in its Research Monograph series as reviewed and submitted by the CPDD. Dr. Louis S. Harris, Department of Pharmacology and Toxicology, Virginia Commonwealth University was the editor of this monograph. COPYRIGHT STATUS The National Institute on Drug Abuse has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required. -
Synthesis and Pharmacological Evaluation of Novel Selective MOR Agonist 6Β-Pyridinyl Amidomorphines Cite This: Med
MedChemComm View Article Online RESEARCH ARTICLE View Journal | View Issue Synthesis and pharmacological evaluation of novel selective MOR agonist 6β-pyridinyl amidomorphines Cite this: Med. Chem. Commun., †‡ 2017, 8,152 exhibiting long-lasting antinociception Ákos Urai,a András Váradi,c Levente Szőcs,a Balázs Komjáti,b Valerie Le Rouzic,c Amanda Hunkele,c Gavril W. Pasternak,c Susruta Majumdarc and Sándor Hosztafi*a It was previously reported that 6β-aminomorphinan derivatives show high affinity for opiate receptors. Novel 6β-heteroarylamidomorphinanes were designed based on the MOR selective antagonist NAP. The 6β-aminomorphinanes were prepared by stereoselective Mitsunobu reaction and subsequently acylated Received 3rd August 2016, with nicotinic acid and isonicotinic acid chloride hydrochlorides. The receptor binding and efficacy were Accepted 4th October 2016 determined in vitro and the analgesic activity was studied in vivo.Thein vitro studies revealed moderate se- lectivity for the MOR. At least two compounds in this series exhibited a long-lasting analgesic response DOI: 10.1039/c6md00450d when administered subcutaneously and intracerebroventricularly. When the substances were given intra- Creative Commons Attribution-NonCommercial 3.0 Unported Licence. www.rsc.org/medchemcomm cerebroventricularly to mice, they showed analgesic potency comparable to morphine. Introduction opiate receptors, for example, a selective KOR agonist (nalfurafine),6 a selective MOR antagonist (clocinnamox),7 and The perception of pain is a consequence of several complex a dual KOR/DOR agonist (MP1104).8 Several studies have been neurochemical processes both in the peripheral and central reported about 6β-aminomorphine derivatives developed in or- nervous system. For the treatment of pain, there are several der to achieve higher selectivity to the MOR to mitigate the classes of drugs available. -
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(12) Patent Application Publication (10) Pub. No.: US 2014/0144429 A1 Wensley Et Al
US 2014O144429A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0144429 A1 Wensley et al. (43) Pub. Date: May 29, 2014 (54) METHODS AND DEVICES FOR COMPOUND (60) Provisional application No. 61/887,045, filed on Oct. DELIVERY 4, 2013, provisional application No. 61/831,992, filed on Jun. 6, 2013, provisional application No. 61/794, (71) Applicant: E-NICOTINE TECHNOLOGY, INC., 601, filed on Mar. 15, 2013, provisional application Draper, UT (US) No. 61/730,738, filed on Nov. 28, 2012. (72) Inventors: Martin Wensley, Los Gatos, CA (US); Publication Classification Michael Hufford, Chapel Hill, NC (US); Jeffrey Williams, Draper, UT (51) Int. Cl. (US); Peter Lloyd, Walnut Creek, CA A6M II/04 (2006.01) (US) (52) U.S. Cl. CPC ................................... A6M II/04 (2013.O1 (73) Assignee: E-NICOTINE TECHNOLOGY, INC., ( ) Draper, UT (US) USPC ..................................................... 128/200.14 (21) Appl. No.: 14/168,338 (57) ABSTRACT 1-1. Provided herein are methods, devices, systems, and computer (22) Filed: Jan. 30, 2014 readable medium for delivering one or more compounds to a O O Subject. Also described herein are methods, devices, systems, Related U.S. Application Data and computer readable medium for transitioning a Smoker to (63) Continuation of application No. PCT/US 13/72426, an electronic nicotine delivery device and for Smoking or filed on Nov. 27, 2013. nicotine cessation. Patent Application Publication May 29, 2014 Sheet 1 of 26 US 2014/O144429 A1 FIG. 2A 204 -1 2O6 Patent Application Publication May 29, 2014 Sheet 2 of 26 US 2014/O144429 A1 Area liquid is vaporized Electrical Connection Agent O s 2. -
[email protected]
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author J Psychopharmacol Manuscript Author . Author Manuscript Author manuscript; available in PMC 2016 October 22. Published in final edited form as: J Psychopharmacol. 2015 July ; 29(7): 812–821. doi:10.1177/0269881115586937. Combined administration of buprenorphine and naltrexone produces antidepressant-like effects in mice Abdulrahman Almatroudi, Stephen M. Husbands, Christopher P. Bailey, and Sarah J. Bailey Department of Pharmacy and Pharmacology, University of Bath, Bath UK Abstract Opiates have been used historically for the treatment of depression. Renewed interest in the use of opiates as antidepressants has focussed on the development of kappa opioid receptor (κ-receptor) antagonists. Buprenorphine acts as a partial μ-opioid receptor agonist and a κ-receptor antagonist. By combining buprenorphine with the opioid antagonist naltrexone, the activation of μ-opioid receptors would be reduced and the κ-antagonist properties enhanced. We have established that a combination dose of buprenorphine (1mg/kg) with naltrexone (1mg/kg) functions as a short-acting κ-antagonist in the mouse tail withdrawal test. Furthermore, this dose combination is neither rewarding nor aversive in the conditioned place preference paradigm and is without significant locomotor effects. We have shown for the first time that systemic co-administration of buprenorphine (1mg/kg) with naltrexone (1mg/kg) in CD-1 mice produced significant antidepressant-like responses in behaviours in both the forced swim test and novelty induced hypophagia task. Behaviours in the elevated plus maze and light dark box were not significantly altered by treatment with buprenorphine alone, or in combination with naltrexone. We propose that the combination of buprenorphine with naltrexone represents a novel, and potentially a readily translatable approach, to the treatment of depression. -
ATP, 489 Absolute Configuration Benzomotphans, 204 Levotphanol
Index AIDA, 495 Affinity labeling, analogs of (Cont.) cAMP, 409, 489 motphine,448 ATP, 409, 489 naltrexone, 449 [3H] ATP, 489 norlevotphanol,449 Absolute configuration normetazocine, 181 benzomotphans, 204 norpethidine, 232 levotphanol, 115 oripavine, 453 methadone and analogs, 316 oxymotphone, 449 motphine, 86 K-Agonists, 179,405,434 phenoperidine, 234 Aid in Interactive Drug Analysis, 495 piperazine derivatives, 399 [L-Ala2] dermotphin, 363 prodines and analogs, 272 [D-Ala, D-Leu] enkephalin (DADL), 68, 344 sinomenine, 28, 115 [D-Ala2 , Bugs] enkephalinamide, 347, 447 viminol, 400 [D-Ala2, Met'] enkephalinamide, 337, 346, Ac 61-91,360 371,489 Acetylcholine, 5, 407 [D-Ala2]leu-enkephalin, 344, 346, 348 Acetylcholine analogs, 186, 191 [D-Ala2] met-enkephalin, 348 l-Acetylcodeine, 32 [D-Ala2] enkephalins, 347 Acetylmethadols (a and (3) Alfentanil, 296 maintenance of addicts by a-isomer, 304, 309 (±)-I1(3-Alkylbenzomotphans, 167, 170 metabolism, 309 11(3-Alkylbenzomotphans, 204 N-allyl and N-CPM analogs, 310, 431 7-Alkylisomotphinans, 146 stereochemistry, 323 N-Alkylnorketobemidones, 431 synthesis, 309 N-Alkylnorpethidines, 233 X-ray crystallography, 327 N-Allylnormetazocine, 420 6-Acetylmotphine, receptor binding, 27 N-Allylnormotphine, 405 Acetylnormethadol, 323 N-Allylnorpethidine, 233 8(3-Acyldihydrocodeinones, 52 3-Allylprodines (a and (3), 256 14-Acyl-4,5-epoxymotphinans, 58 'H-NMR and stereochemistry, 256 7-Acylhydromotphones, 128 X-ray crystallography, 256 Addiction, 4 N-Allylnormetazocine, 420 Adenylate cyclase, 6, 409, 413, 424,