A Guide to Medications Inducing Salivary Gland Dysfunction
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Drug Development for the Irritable Bowel Syndrome: Current Challenges and Future Perspectives
REVIEW ARTICLE published: 01 February 2013 doi: 10.3389/fphar.2013.00007 Drug development for the irritable bowel syndrome: current challenges and future perspectives Fabrizio De Ponti* Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy Edited by: Medications are frequently used for the treatment of patients with the irritable bowel syn- Angelo A. Izzo, University of Naples drome (IBS), although their actual benefit is often debated. In fact, the recent progress in Federico II, Italy our understanding of the pathophysiology of IBS, accompanied by a large number of preclin- Reviewed by: Elisabetta Barocelli, University of ical and clinical studies of new drugs, has not been matched by a significant improvement Parma, Italy of the armamentarium of medications available to treat IBS. The aim of this review is to Raffaele Capasso, University of outline the current challenges in drug development for IBS, taking advantage of what we Naples Federico II, Italy have learnt through the Rome process (Rome I, Rome II, and Rome III). The key questions *Correspondence: that will be addressed are: (a) do we still believe in the “magic bullet,” i.e., a very selective Fabrizio De Ponti, Pharmacology Unit, Department of Medical and Surgical drug displaying a single receptor mechanism capable of controlling IBS symptoms? (b) IBS Sciences, University of Bologna, Via is a “functional disorder” where complex neuroimmune and brain-gut interactions occur Irnerio, 48, 40126 Bologna, Italy. and minimal inflammation is often documented: -
Peripheral Kappa Opioid Receptor Activation Drives Cold Hypersensitivity in Mice
bioRxiv preprint doi: https://doi.org/10.1101/2020.10.04.325118; this version posted October 4, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Peripheral kappa opioid receptor activation drives cold hypersensitivity in mice Manish K. Madasu1,2,3, Loc V. Thang1,2,3, Priyanka Chilukuri1,3, Sree Palanisamy1,2, Joel S. Arackal1,2, Tayler D. Sheahan3,4, Audra M. Foshage3, Richard A. Houghten6, Jay P. McLaughlin5.6, Jordan G. McCall1,2,3, Ream Al-Hasani1,2,3 1Center for Clinical Pharmacology, St. Louis College of Pharmacy and Washington University School of Medicine, St. Louis, MO, USA. 2Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, MO, USA 3Department of Anesthesiology, Pain Center, Washington University. St. Louis, MO, USA. 4 Division of Biology and Biomedical Science, Washington University in St. Louis, MO, USA 5Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA 6Torrey Pines Institute for Molecular Studies, Port St. Lucie, FL, USA Corresponding Author: Dr. Ream Al-Hasani Center for Clinical Pharmacology St. Louis College of Pharmacy Washington University School of Medicine 660 South Euclid Campus Box 8054 St. Louis MO, 63110 [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2020.10.04.325118; this version posted October 4, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
Curriculum Vitae: Lin Chang
CURRICULUM VITAE LIN CHANG, M.D. Professor of Medicine Vatche and Tamar Manoukian Division of Digestive Diseases David Geffen School of Medicine at UCLA PERSONAL HISTORY: Office Address: G. Oppenheimer Center for Neurobiology of Stress and Resilience 10833 Le Conte Avenue CHS 42-210 Los Angeles, CA 90095-7378 (310) 206-0192; FAX (310) 825-1919 EDUCATION: 1978 - 1982 University of California, Los Angeles, Degree: B.S. Biochemistry 1982 - 1986 UCLA School of Medicine, Los Angeles, Degree: M.D. 1986 - 1987 Internship: Harbor-UCLA Medical Center, Internal Medicine 1987 - 1989 Residency: Harbor-UCLA Medical Center, Internal Medicine 1989 - 1990 Research Fellowship: Harbor-UCLA Medical Center, Division of Gastroenterology 1990 - 1992 Clinical Fellowship: UCLA Integrated Program, Gastroenterology BOARD CERTIFICATION: ABIM: Internal Medicine 1989 Gastroenterology 1993, recertification 2014 PROFESSIONAL EXPERIENCE: 2006- present Professor of Medicine-in-Residence, Division of Digestive Diseases, David Geffen School of Medicine at UCLA 2000 - 2006 Associate Professor of Medicine, Division of Digestive Diseases, David Geffen School of Medicine at UCLA 1997 - 2000 Assistant Professor of Medicine, Division of Digestive Diseases, UCLA School of Medicine Chang 2 1993 - 1997 Assistant Professor of Medicine-in-Residence, UCLA, Harbor-UCLA Medical Center 1992 - 1993 Associate Consultant, Mayo Clinic, Rochester, Minnesota, Department of Gastroenterology PROFESSIONAL ACTIVITIES: 2017 – present Vice-Chief, Vatche and Tamar Manoukian Division of Digestive -
(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. -
Use of Compounds That Are Effective As Selective
(19) & (11) EP 1 505 974 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 31/445 (2006.01) A61K 31/40 (2006.01) 22.04.2009 Bulletin 2009/17 A61K 31/485 (2006.01) A61K 31/135 (2006.01) A61P 3/04 (2006.01) (21) Application number: 03752716.5 (86) International application number: (22) Date of filing: 28.04.2003 PCT/EP2003/004428 (87) International publication number: WO 2003/097051 (27.11.2003 Gazette 2003/48) (54) USE OF COMPOUNDS THAT ARE EFFECTIVE AS SELECTIVE OPIATE RECEPTOR MODULATORS VERWENDUNG VON VERBINDUNGEN, DIE ALS SELEKTIVE OPIAT-REZEPTOR- MODULATOREN WIRKSAM SIND UTILISATION DE COMPOSES S’AVERANT EFFICACES EN TANT QUE MODULATEURS SELECTIFS DES RECEPTEURS DES OPIACES (84) Designated Contracting States: (56) References cited: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR WO-A-01/98267 WO-A-02/13801 HU IE IT LI LU MC NL PT RO SE SI SK TR WO-A-03/048113 US-A- 4 889 860 Designated Extension States: US-B1- 6 569 449 LT LV • MORLEY J E ET AL: "EFFECT OF (30) Priority: 17.05.2002 EP 02011047 BUTORPHANOL TARTRATE ON FOOD AND WATER CONSUMPTION IN HUMANS" (43) Date of publication of application: AMERICAN JOURNAL OF CLINICAL NUTRITION, 16.02.2005 Bulletin 2005/07 vol. 42, no. 6, 1985, pages 1175-1178, XP008022098 ISSN: 0002-9165 (73) Proprietor: Tioga Pharmaceuticals, Inc. • MENDELSON SCOTT D: "Treatment of anorexia San Diego, CA 92121 (US) nervosa with tramadol." AMERICAN JOURNAL OF PSYCHIATRY, vol. -
Association Between N-Desmethylclozapine and Clozapine-Induced Sialorrhea
JPET Fast Forward. Published on August 29, 2020 as DOI: 10.1124/jpet.120.000164 This article has not been copyedited and formatted. The final version may differ from this version. 1 Title page Association between N-desmethylclozapine and clozapine-induced sialorrhea: Involvement of increased nocturnal salivary secretion via muscarinic receptors by N- desmethylclozapine Downloaded from Authors and Affiliations: Shuhei Ishikawa, PhD1, 2, a, Masaki Kobayashi, PhD1, 3, *, Naoki Hashimoto, PhD, jpet.aspetjournals.org MD4, Hideaki Mikami, BPharm1, Akihiko Tanimura, PhD5, Katsuya Narumi, PhD1, Ayako Furugen, PhD1, Ichiro Kusumi, PhD, MD4, and Ken Iseki, PhD1 at ASPET Journals on September 23, 2021 1 Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University 2 Department of Pharmacy, Hokkaido University Hospital 3 Education Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokkaido University 4 Department of Psychiatry, Hokkaido University Graduate School of Medicine 5 Department of Pharmacology, School of Dentistry, Health Sciences University of Hokkaido a Present address: Department of Psychiatry, Hokkaido University Hospital JPET Fast Forward. Published on August 29, 2020 as DOI: 10.1124/jpet.120.000164 This article has not been copyedited and formatted. The final version may differ from this version. 2 Running title page Association between N-desmethylclozapine and CIS Corresponding author: Masaki Kobayashi Downloaded from Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, jpet.aspetjournals.org Kita-ku, Sapporo 060-0812, Japan. Phone/Fax: +81-11-706-3772/3235. E-mail: [email protected] at ASPET Journals on September 23, 2021 Number of text pages: 25 Number of tables: 1 Number of figures: 6 Number of words in the Abstract: 249 Number of words in the Introduction: 686 Number of words in the Discussion: 1492 JPET Fast Forward. -
Guideline for Opioid Therapy and Chronic Noncancer Pain
GUIDELINE CPD Guideline for opioid therapy and chronic noncancer pain Jason W. Busse DC PhD, Samantha Craigie MSc, David N. Juurlink MD PhD, D. Norman Buckley MD, Li Wang PhD, Rachel J. Couban MA MISt, Thomas Agoritsas MD PhD, Elie A. Akl MD PhD, Alonso Carrasco-Labra DDS MSc, Lynn Cooper BES, Chris Cull, Bruno R. da Costa PT PhD, Joseph W. Frank MD MPH, Gus Grant AB LLB MD, Alfonso Iorio MD PhD, Navindra Persaud MD MSc, Sol Stern MD, Peter Tugwell MD MSc, Per Olav Vandvik MD PhD, Gordon H. Guyatt MD MSc n Cite as: CMAJ 2017 May 8;189:E659-66. doi: 10.1503/cmaj.170363 CMAJ podcasts: author interview at https://soundcloud.com/cmajpodcasts/170363-guide See related article www.cmaj.ca/lookup/doi/10.1503/cmaj.170431 hronic noncancer pain includes any painful condition that persists for at least three months and is not associated KEY POINTS with malignant disease.1 According to seven national sur- • We recommend optimization of nonopioid pharmacotherapy Cveys conducted between 1994 and 2008, 15%–19% of Canadian and nonpharmacologic therapy, rather than a trial of opioids, adults live with chronic noncancer pain.2 Chronic noncancer pain for patients with chronic noncancer pain. interferes with activities of daily living, has a major negative • Patients with chronic noncancer pain may be offered a trial of impact on quality of life and physical function,3 and is the leading opioids only after they have been optimized on nonopioid cause of health resource utilization and disability among working - therapy, including nondrug measures. age adults.4,5 • We suggest avoiding opioid therapy for patients with a history of In North America, clinicians commonly prescribe opioids for substance use disorder (including alcohol) or active mental illness, and opioid therapy should be avoided in cases of active substance acute pain, palliative care (in particular, for patients with cancer) use disorder. -
Rapid and Robust Analysis Method for Quantifying Antidepressants and Major Metabolites in Human Serum by UHPLC-MS/MS
PO-CON1352E Rapid and Robust Analysis Method for Quantifying Antidepressants and Major Metabolites in Human Serum by UHPLC-MS/MS ASMS 2013 WP-095 Vincent Goudriaan1, Christ Pijnenburg2, Jacob Diepenbroek2, Jan Giesbertsen2, Annemieke Vermeulen Windsant-v.d. Tweel2 1Shimadzu Benelux BV, ‘s-Hertogenbosch, Netherlands. 2ZANOB BV, ‘s-Hertogenbosch, Netherlands. Rapid and Robust Analysis Method for Quantifying Antidepressants and Major Metabolites in Human Serum by UHPLC-MS/MS 1. Introduction Therapeutic drug monitoring (TDM) of antidepressants is administered drugs, metabolites or endogenic compounds. one of the most widely utilized analysis in clinical labs in UHPLC-MS/MS is much more sensitive, more selective, and Dutch hospitals nowadays. Traditionally quantitation of if robust the perfect replacement of routine HPLC analysis. antidepressants is performed by means of HPLC with Due to simplified sample prep, faster analysis and less diode-array detection (DAD). Obvious disadvantages of the solvent consumption UHPLC-MS/MS is much more cost latter method are: sensitivity, selectivity and possibility of effective. UHPLC-MS/MS methods will replace routine HPLC false positives as a result of co-elution with other methods in clinical labs. 2. Methods and Materials Human serum samples were extracted by means of off-line solid phase extraction. The extracts were analyzed with a Shimadzu Nexera UHPLC combined with a LCMS-8040 Tandem Mass Spectrometer. 5 µL of sample was injected with a SIL-30AC autosampler. 2-1. Sample Preparation Standards both for calibration and control are ready made serum standards. The standards are pretreated in the same way as the samples. 1. Precondition SPE material1 with 1 mL 3% ammonia in acetonitrile 2. -
(12) Patent Application Publication (10) Pub. No.: US 2011/0245287 A1 Holaday Et Al
US 20110245287A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0245287 A1 Holaday et al. (43) Pub. Date: Oct. 6, 2011 (54) HYBRD OPOD COMPOUNDS AND Publication Classification COMPOSITIONS (51) Int. Cl. A6II 3/4748 (2006.01) C07D 489/02 (2006.01) (76) Inventors: John W. Holaday, Bethesda, MD A6IP 25/04 (2006.01) (US); Philip Magistro, Randolph, (52) U.S. Cl. ........................................... 514/282:546/45 NJ (US) (57) ABSTRACT Disclosed are hybrid opioid compounds, mixed opioid salts, (21) Appl. No.: 13/024,298 compositions comprising the hybrid opioid compounds and mixed opioid salts, and methods of use thereof. More particu larly, in one aspect the hybrid opioid compound includes at (22) Filed: Feb. 9, 2011 least two opioid compounds that are covalently bonded to a linker moiety. In another aspect, the hybrid opioid compound relates to mixed opioid salts comprising at least two different Related U.S. Application Data opioid compounds or an opioid compound and a different active agent. Also disclosed are pharmaceutical composi (60) Provisional application No. 61/302,657, filed on Feb. tions, as well as to methods of treating pain in humans using 9, 2010. the hybrid compounds and mixed opioid salts. Patent Application Publication Oct. 6, 2011 Sheet 1 of 3 US 2011/0245287 A1 Oral antinociception of morphine, oxycodone and prodrug combinations in CD1 mice s Tigkg -- Morphine (2.80 mg/kg (1.95 - 4.02, 30' peak time -- (Oxycodone (1.93 mg/kg (1.33 - 2,65)) 30 peak time -- Oxy. Mor (1:1) (4.84 mg/kg (3.60 - 8.50) 60 peak tire --MLN 2-3 peak, effect at a hors 24% with closes at 2.5 art to rigg - D - MLN 2-45 (6.60 mg/kg (5.12 - 8.51)} 60 peak time Figure 1. -
Screening of 300 Drugs in Blood Utilizing Second Generation
Forensic Screening of 300 Drugs in Blood Utilizing Exactive Plus High-Resolution Accurate Mass Spectrometer and ExactFinder Software Kristine Van Natta, Marta Kozak, Xiang He Forensic Toxicology use Only Drugs analyzed Compound Compound Compound Atazanavir Efavirenz Pyrilamine Chlorpropamide Haloperidol Tolbutamide 1-(3-Chlorophenyl)piperazine Des(2-hydroxyethyl)opipramol Pentazocine Atenolol EMDP Quinidine Chlorprothixene Hydrocodone Tramadol 10-hydroxycarbazepine Desalkylflurazepam Perimetazine Atropine Ephedrine Quinine Cilazapril Hydromorphone Trazodone 5-(p-Methylphenyl)-5-phenylhydantoin Desipramine Phenacetin Benperidol Escitalopram Quinupramine Cinchonine Hydroquinine Triazolam 6-Acetylcodeine Desmethylcitalopram Phenazone Benzoylecgonine Esmolol Ranitidine Cinnarizine Hydroxychloroquine Trifluoperazine Bepridil Estazolam Reserpine 6-Monoacetylmorphine Desmethylcitalopram Phencyclidine Cisapride HydroxyItraconazole Trifluperidol Betaxolol Ethyl Loflazepate Risperidone 7(2,3dihydroxypropyl)Theophylline Desmethylclozapine Phenylbutazone Clenbuterol Hydroxyzine Triflupromazine Bezafibrate Ethylamphetamine Ritonavir 7-Aminoclonazepam Desmethyldoxepin Pholcodine Clobazam Ibogaine Trihexyphenidyl Biperiden Etifoxine Ropivacaine 7-Aminoflunitrazepam Desmethylmirtazapine Pimozide Clofibrate Imatinib Trimeprazine Bisoprolol Etodolac Rufinamide 9-hydroxy-risperidone Desmethylnefopam Pindolol Clomethiazole Imipramine Trimetazidine Bromazepam Felbamate Secobarbital Clomipramine Indalpine Trimethoprim Acepromazine Desmethyltramadol Pipamperone -
WO 2012/109445 Al 16 August 2012 (16.08.2012) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2012/109445 Al 16 August 2012 (16.08.2012) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 31/485 (2006.01) A61P 25/04 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, (21) International Application Number: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, PCT/US20 12/024482 DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (22) International Filing Date: HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, ' February 2012 (09.02.2012) KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (25) Filing Language: English OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, (26) Publication Language: English SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 13/024,298 9 February 201 1 (09.02.201 1) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant (for all designated States except US): QRX- GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, PHARMA LTD.