A Randomised Controlled Trial of Absorbatox™ C35 in Irritable Bowel
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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: -
Current Neuropharmacology, 2016, 14, 842-856
842 Send Orders for Reprints to [email protected] Current Neuropharmacology, 2016, 14, 842-856 REVIEW ARTICLE ISSN: 1570-159X eISSN: 1875-6190 Impact Factor: Pathogenesis, Experimental Models and Contemporary Pharmacotherapy 3.753 of Irritable Bowel Syndrome: Story About the Brain-Gut Axis BENTHAM SCIENCE S.W. Tsang1, K.K.W. Auyeung1, Z.X. Bian2,3 and J.K.S. Ko1,3,* 1Teaching and Research Division, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China; 2Clinical Division, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China; 3Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China Abstract: Background: Although the precise pathophysiology of irritable bowel syndrome (IBS) remains unknown, it is generally considered to be a disorder of the brain-gut axis, representing the disruption of communication between the brain and the digestive system. The present review describes advances in understanding the pathophysiology and experimental approaches in studying IBS, as well as providing an update of the therapies targeting brain-gut axis in the treatment of the disease. Methods: Causal factors of IBS are reviewed. Following this, the preclinical experimental models of IBS will be introduced. Besides, both current and future A R T I C L E H I S T O R Y therapeutic approaches of IBS will be discussed. J.K.S. Ko Received: September 24, 2015 Revised: February 07, 2016 Results: When signal of the brain-gut axis becomes misinterpreted, it may lead to dysregulation of both Accepted: March 22, 2016 central and enteric nervous systems, altered intestinal motility, increased visceral sensitivity and DOI: consequently contributing to the development of IBS. -
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 -
Guideline the 2017 Canadian Guideline for Opioids for Chronic
The 2017 Canadian Guideline for Opioids for Chronic Non-Cancer Pain Main editor Publishing Information Jason Busse Associate Professor, Department of Anesthesia, Associate v4.10 published on 29.10.2018 Professor, Department of Health Research Methods, Evidence and Impact McMaster University, HSC-2V9, 1280 Main St. West, Hamilton, Ontario, Canada, L8S 4K1 [email protected] National pain center 1 of 106 The 2017 Canadian 2017 Guideline Canadian for Opioids for Chronic Non-CancerGuideline Pain - National painfor center Opioids for Chronic Non-Cancer Pain Guideline Panel Members: Jason W. Busse (Chair), McMaster University, Canada Gordon H. Guyatt, McMaster University, Canada Alonso Carrasco, American Dental Association, USA Elie Akl, American University of Beirut, Lebanon Thomas Agoritsas, University Hospitals of Geneva, Switzerland Bruno da Costa, Florida International University, USA Per Olav Vandvik, Innlandet Hospital Trust-Division Gjøvik, Norway Peter Tugwell, University of Ottawa, Canada Sol Stern, private practice, Canada Lynn Cooper, Canadian Pain Coalition, Canada Chris Cull, Inspire by Example, Canada Gus Grant, College of Physicians and Surgeons of Nova Scotia, Canada Alfonso Iorio, McMaster University, Canada Nav Persaud, University of Toronto, Canada Joseph Frank, VA Eastern Colorado Health Care System, USA Guideline Steering Committee: Gordon H. Guyatt (Chair), Norm Buckley, Jason W. Busse, David Juurlink Clinical Expert Committee: Norm Buckley, Donna Buna, Gary Franklin, Chris Giorshev, Jeff Harris, Lydia Hatcher, Kurt Hegmann, Roman Jovey, David Juurlink, Priya Manjoo, Pat Morley-Forster, Dwight Moulin, Mark Sullivan Patient Advisory Committee:* Bart Bennett, Lynn Cooper, Chris Cull, Ada Giudice-Tompson, Deborah Ironbow, Pamela Jessen, Mechelle Kane, Andrew Koster, Sue Mace, Tracy L. Mercer, Kyle Neilsen, Ian Tregunna, Jen Watson * 3 members did not provide written consent to be listed Evidence Synthesis Team: Samantha Craigie, Jason W. -
United States Patent (10) Patent No.: US 8,969,514 B2 Shailubhai (45) Date of Patent: Mar
USOO896.9514B2 (12) United States Patent (10) Patent No.: US 8,969,514 B2 Shailubhai (45) Date of Patent: Mar. 3, 2015 (54) AGONISTS OF GUANYLATECYCLASE 5,879.656 A 3, 1999 Waldman USEFUL FOR THE TREATMENT OF 36; A 6. 3: Watts tal HYPERCHOLESTEROLEMIA, 6,060,037- W - A 5, 2000 Waldmlegand et al. ATHEROSCLEROSIS, CORONARY HEART 6,235,782 B1 5/2001 NEW et al. DISEASE, GALLSTONE, OBESITY AND 7,041,786 B2 * 5/2006 Shailubhai et al. ........... 530.317 OTHER CARDOVASCULAR DISEASES 2002fOO78683 A1 6/2002 Katayama et al. 2002/O12817.6 A1 9/2002 Forssmann et al. (75) Inventor: Kunwar Shailubhai, Audubon, PA (US) 2003,2002/0143015 OO73628 A1 10/20024, 2003 ShaubhaiFryburg et al. 2005, OO16244 A1 1/2005 H 11 (73) Assignee: Synergy Pharmaceuticals, Inc., New 2005, OO32684 A1 2/2005 Syer York, NY (US) 2005/0267.197 A1 12/2005 Berlin 2006, OO86653 A1 4, 2006 St. Germain (*) Notice: Subject to any disclaimer, the term of this 299;s: A. 299; NS et al. patent is extended or adjusted under 35 2008/0137318 A1 6/2008 Rangarajetal.O U.S.C. 154(b) by 742 days. 2008. O151257 A1 6/2008 Yasuda et al. 2012/O196797 A1 8, 2012 Currie et al. (21) Appl. No.: 12/630,654 FOREIGN PATENT DOCUMENTS (22) Filed: Dec. 3, 2009 DE 19744O27 4f1999 (65) Prior Publication Data WO WO-8805306 T 1988 WO WO99,26567 A1 6, 1999 US 2010/O152118A1 Jun. 17, 2010 WO WO-0 125266 A1 4, 2001 WO WO-02062369 A2 8, 2002 Related U.S. -
The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments
J Neurogastroenterol Motil, Vol. 22 No. 4 October, 2016 pISSN: 2093-0879 eISSN: 2093-0887 http://dx.doi.org/10.5056/jnm16001 JNM Journal of Neurogastroenterology and Motility Review The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments Mohammad H Farzaei,1,2 Roodabeh Bahramsoltani,3 Mohammad Abdollahi,3,4* and Roja Rahimi5* 1Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; 2Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; 3Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran; 4Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; and 5Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran Irritable bowel syndrome (IBS) is the most common disorder referred to gastroenterologists and is characterized by altered bowel habits, abdominal pain, and bloating. Visceral hypersensitivity (VH) is a multifactorial process that may occur within the peripheral or central nervous systems and plays a principal role in the etiology of IBS symptoms. The pharmacological studies on selective drugs based on targeting specific ligands can provide novel therapies for modulation of persistent visceral hyperalgesia. The current paper reviews the cellular and molecular mechanisms underlying therapeutic targeting for providing future drugs to protect or treat visceroperception and pain sensitization in IBS patients. There are a wide range of mediators and receptors participating in visceral pain perception amongst which substances targeting afferent receptors are attractive sources of novel drugs. Novel therapeutic targets for the management of VH include compounds which alter gut-brain pathways and local neuroimmune pathways. -
(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. -
)&F1y3x PHARMACEUTICAL APPENDIX to THE
)&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE -
X351endoscopic Ultrasonography and Computed
3rd UEGWOslo 1994 A9 viding the patients according to the criteria of Colin-Jones gave very small -8%, 95% Cl -22% to +7%). The response was unrelated to subgroups of groups and offered no further information. The effects of the drug on individ- dyspepsia: effects of CIS, NIZ and PLA, respectively, in R: 57%, 60%, and ual symptoms, likewise, did not reach significance. 74%, in D: 61%, 55%, and 55%, in U: 67%, 50%, and 60% and in I: 67%, Gut: first published as 10.1136/gut.35.4_Suppl.A9 on 1 January 1994. Downloaded from Conclusion: Our results do not support a role for gastric acid production 50%, and 64%. in generation of functional upper dyspepsia and do not warrant prescription Conclusion: effects of a 2-week course of CIS or NIZ in unselected patients of Omeprazole to patients suffering from non-ulcer dyspepsia. with NUD were not superior to effects of PLA. Symptom grouping was not predictive of response to therapy. 3 Effects of Fedotozine in Chronic Idiopathic Dyspepsia: A Double Blind, Placebo Controlled 351EndoscopicX Ultrasonography and Computed Multicentre Study Tomography in Diagnosis and Staging of Pancreatic Tumors: Comparison with Surgery J.P Galmiche 1, C. de Meynard 2, J.L. Abitbol 2, B. Scherrer2, B. Fraitag 2. 1 Service d'H6pato-Gastroent6rologie, CHU Nord, BP 1005, 44035 Nantes; J.M. Aubertin 1, 0. Marty1, J.L. Bouillot2, A. Hernigou3, F. Bloch 1, J.P 2 Institut de Recherche Jouveinal, BP 100, 94265 Fresnes Petite 1. 1 Dept of Gastroenterology, H6pital Broussais, 75014 Paris, France; 2 Dept ofSurgery, H6pital Broussais, 75014 Paris, France; 3 Dept of Safety and efficacy of fedotozine (F), a peripheral K agonist, were assessed Radiology, H6pital Broussais, 75014 Paris, France versus placebo (P), in a double blind multicentre study conducted in France by hospital and private gastroenterologists. -
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.