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(12) Patent Application Publication (10) Pub. No.: US 2013/0253056A1 Nemas Et Al
US 20130253 056A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0253056A1 Nemas et al. (43) Pub. Date: Sep. 26, 2013 (54) CONTINUOUS ADMINISTRATION OF (60) Provisional application No. 61/179,511, filed on May LEVODOPA AND/OR DOPA 19, 2009. DECARBOXYLASE INHIBITORS AND COMPOSITIONS FOR SAME Publication Classification (71) Applicant: NEURODERM, LTD., Ness-Ziona (IL) (51) Int. Cl. A63L/216 (2006.01) (72) Inventors: Mara Nemas, Gedera (IL); Oron (52) U.S. Cl. Yacoby-Zeevi, Moshav Bitsaron (IL) CPC .................................... A6 IK3I/216 (2013.01) USPC .......................................................... 514/538 (73) Assignee: Neuroderm, Ltd., Ness-Ziona (IL) (57) ABSTRACT (21) Appl. No.: 13/796,232 Disclosed herein are for example, liquid aqueous composi (22) Filed: Mar 12, 2013 tions that include for example an ester or salt of levodopa, or an ester or salt of carbidopa, and methods for treating neuro Related U.S. Application Data logical or movement diseases or disorders such as restless leg (63) Continuation-in-part of application No. 12/961,534, syndrome, Parkinson's disease, secondary parkinsonism, filed on Dec. 7, 2010, which is a continuation of appli Huntington's disease, Parkinson's like syndrome, PSP. MSA, cation No. 12/836,130, filed on Jul. 14, 2010, now Pat. ALS, Shy-Drager syndrome, dystonia, and conditions result No. 7,863.336, which is a continuation of application ing from brain injury including carbon monoxide or manga No. 12/781,357, filed on May 17, 2010, now Pat. No. nese intoxication, using Substantially continuous administra 8,193,243. tion of levodopa and/or carbidopa or ester and/or salt thereof. -
TR-348: Alpha-Methyldopa Sesquihydrate (CASRN 41372-08-1)
NATIONAL TOXICOLOGY PROGRAM Technical Report Series No. 348 TOXICOLOGY AND CARCINOGENESIS STUDIES OF a/pha-METHYLDOPA SESQUIHYDRATE (CAS NO. 41372-08-1) IN F344/N RATS AND B6C3Fi MICE (FEED STUDIES) U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health NTP TECHNICAL REPORT ON THE TOXICOLOGY AND CARCINOGENESIS STUDIES OF a/p/)a-METHYLDOPA SESQUIHYDRATE (CAS NO. 41372-08-1) IN F344/N RATS AND B6C3Fi MICE (FEED STUDIES) June K. Dunnick, Ph.D., Chemical Manager NATIONAL TOXICOLOGY PROGRAM P.O. Box 12233 Research Triangle Park, NC 27709 March 1989 NTP TR 348 NIH Publication No. 89-2803 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health NOTE TO THE READER This study was performed under the direction of the K’ational Institute of Environmental Health Sci- ences as a function of the National Toxicology Program. The studies described in this Technical Re- port have been conducted in compliance with NTP chemical health and safety requirements and must meet or exceed all applicable Federal, state, and local health and safety regulations. Animal care and use were in accordance with the U.S. Public Health Service Policy on Humane Care and Use of Ani- mals. All NTP toxicology and carcinogenesis studies are subjected to a data audit before being pre- sented for public peer review. Although every effort is made to prepare the Technical Reports as accurately as possible, mistakes may occur. Readers are requested to identify any mistakes so that corrective action may be taken. Further, anyone who is aware of related ongoing or published studies not mentioned in this report is encouraged to make this information known to the NTP. -
Parkinson Disease-Associated Cognitive Impairment
PRIMER Parkinson disease-associated cognitive impairment Dag Aarsland 1,2 ✉ , Lucia Batzu 3, Glenda M. Halliday 4, Gert J. Geurtsen 5, Clive Ballard 6, K. Ray Chaudhuri 3 and Daniel Weintraub7,8 Abstract | Parkinson disease (PD) is the second most common neurodegenerative disorder, affecting >1% of the population ≥65 years of age and with a prevalence set to double by 2030. In addition to the defining motor symptoms of PD, multiple non-motor symptoms occur; among them, cognitive impairment is common and can potentially occur at any disease stage. Cognitive decline is usually slow and insidious, but rapid in some cases. Recently, the focus has been on the early cognitive changes, where executive and visuospatial impairments are typical and can be accompanied by memory impairment, increasing the risk for early progression to dementia. Other risk factors for early progression to dementia include visual hallucinations, older age and biomarker changes such as cortical atrophy, as well as Alzheimer-type changes on functional imaging and in cerebrospinal fluid, and slowing and frequency variation on EEG. However, the mechanisms underlying cognitive decline in PD remain largely unclear. Cortical involvement of Lewy body and Alzheimer-type pathologies are key features, but multiple mechanisms are likely involved. Cholinesterase inhibition is the only high-level evidence-based treatment available, but other pharmacological and non-pharmacological strategies are being tested. Challenges include the identification of disease-modifying therapies as well as finding biomarkers to better predict cognitive decline and identify patients at high risk for early and rapid cognitive impairment. Parkinson disease (PD) is the most common movement The full spectrum of cognitive impairment occurs in disorder and the second most common neurodegenera individuals with PD, from subjective cognitive decline tive disorder after Alzheimer disease (AD). -
A Quick Guide to Drugs and Alcohol
A QUICK GUIDE TO Drugs & Alcohol THIRD EDITION by the National Drug and Alcohol Research Centre (NDARC) Drug Info is a partnership between the State Library of New South Wales and NSW Health. www.druginfo.sl.nsw.gov.au Disclaimer The contents of this book are intended for information purposes only. Every efort has been made to ensure that the information is correct at the time of publication. Drug Info does not ofer any information in this book as a tool for treatment, counselling or legal advice. Drug Info recommends that prior to making any decision based on any information in this book, you should obtain independent professional legal or medical advice. Websites and information about service providers referred to in the publication have been selected to provide relevant and up-to-date information as at the date of publication. Drug Info accepts no responsibility for the content of websites and does not endorse any specifc services ofered by providers. A Quick Guide to Drugs & Alcohol, third edition, September 2017 Published by Drug Info, State Library of NSW © Copyright Library Council of NSW and NSW Ministry of Health, 2017 ISBN 0 7313 7239 5 (print) ISBN 0 7313 7240 9 (online) Printed in Australia by SEED Print, using Spicers Paper Monza Recycled Satin 350 gsm and Impress Matt 115 gsm. Monza Recycled contains 99% recycled fbre and is FSC® Mix Certifed, Impress Matt is FSC® Mix Certifed. P&D-4660-9/2017 ECSTASY E, pills, eccy, XTC, MDMA, pingas, Adam, X 7 Ecstasy is a derivative of methamphetamine (the active ingredient is 3, 4-methylenedioxymethamphetamine, abbreviated to MDMA). -
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. -
NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Amphetamine and Methamphetamine
Published 2005 Wiley-Liss, Inc.w Birth Defects Research (Part B) 74:471–584 (2005) NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity Of Amphetamine and Methamphetamine Mari Golub,1 Lucio Costa,2 Kevin Crofton,3 Deborah Frank,4 Peter Fried,5 Beth Gladen6 Rogene Henderson,7 Erica Liebelt,8 Shari Lusskin,9 Sue Marty,10 Andrew Rowland11 John Scialli12 and Mary Vore13 1California Environment Protection Agency, Sacramento, California 2University of Washington, Seattle, Washington 3U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 4Boston Medical Center, Boston, Massachusetts 5Carleton University, Ottawa, Ontario 6National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 7Lovelace Respiratory Research Institute, Albuquerque, New Mexico 8University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 9New York University School of Medicine, New York, New York 10The Dow Chemical Company, Midland, Michigan 11University of New Mexico, Albuquerque, New Mexico 12Phoenix, Arizona 13University of Kentucky, Lexington, Kentucky PREFACE studies indexed before December 31, 2004. References were also identified from databases such as REPRO- The National Toxicology Program (NTP) and the TOXs, HSDB, IRIS, and DART and from report National Institute of Environmental Health Sciences bibliographies. (NIEHS) established the NTP Center for the Evaluation This evaluation resulted from the efforts of a 13- of Risks to Human Reproduction (CERHR) in June 1998. member panel of government and non-government The purpose of the Center is to provide timely, unbiased, scientists that culminated in a public expert panel scientifically sound evaluations of human and experi- meeting held January 10–12, 2005. This report is a mental evidence for adverse effects on reproduction and product of the Expert Panel and is intended to (1) development caused by agents to which humans may be interpret the strength of scientific evidence that exposed. -
Summary of Product Characteristics
Health Products Regulatory Authority Summary of Product Characteristics 1 NAME OF THE MEDICINAL PRODUCT Salbutamol CFC-Free Inhaler 100 micrograms per metered dose, pressurised inhalation, suspension 2 QUALITATIVE AND QUANTITATIVE COMPOSITION One metered dose contains 100 micrograms of salbutamol (equivalent to 120 micrograms of salbutamol sulphate). This is equivalent to a delivered dose of 90 micrograms of salbutamol (equivalent to 108 micrograms of salbutamol sulphate). For the full list of excipients, see section 6.1. 3 PHARMACEUTICAL FORM Pressurised inhalation suspension Pressurised inhalation suspension supplied in an aluminium canister with a metering valve and a plastic actuator and dust cap. 4 CLINICAL PARTICULARS 4.1 Therapeutic Indications Salbutamol CFC-Free Inhaler is indicated in adults, adolescents and children. For babies and children under 4 years of age, see sections 4.2 and 5.1. Salbutamol CFC-Free Inhaler is indicated for the relief and prevention of bronchial asthma and conditions associated with reversible airways obstruction. Salbutamol CFC-Free Inhaler can be used as relief medication in the management of mild, moderate or severe asthma, provided that its use does not delay the introduction and use of regular inhaled corticosteroid therapy, where necessary. 4.2 Posology and method of administration Salbutamol CFC-Free Inhaler is for oral inhalation use only. Posology Adults (including the elderly) and adolescents (children 12 years and over): For the relief of acute bronchospasm, one inhalation (100 micrograms) increasing to two inhalations (200 micrograms), if necessary. To prevent allergen- or exercise-induced symptoms, two inhalations (200 micrograms) should be taken 10-15 minutes before challenge. Maximum daily dose: two inhalations (200 micrograms) up to four times a day. -
Azilect, INN-Rasagiline
SCIENTIFIC DISCUSSION 1. Introduction AZILECT is indicated for the treatment of idiopathic Parkinson’s disease (PD) as monotherapy (without levodopa) or as adjunct therapy (with levodopa) in patients with end of dose fluctuations. Rasagiline is administered orally, at a dose of 1 mg once daily with or without levodopa. Parkinson’s disease is a common neurodegenerative disorder typified by loss of dopaminergic neurones from the basal ganglia, and by a characteristic clinical syndrome with cardinal physical signs of resting tremor, bradikinesia and rigidity. The main treatment aims at alleviating symptoms through a balance of anti-cholinergic and dopaminergic drugs. Parkinson’s disease (PD) treatment is complex due to the progressive nature of the disease, and the array of motor and non-motor features combined with early and late side effects associated with therapeutic interventions. Rasagiline is a chemical inhibitor of the enzyme monoamine oxidase (MAO) type B which has a major role in the inactivation of biogenic and diet-derived amines in the central nervous system. MAO has two isozymes (types A and B) and type B is responsible for metabolising dopamine in the central nervous system; as dopamine deficiency is the main contributing factor to the clinical manifestations of Parkinson’s disease, inhibition of MAO-B should tend to restore dopamine levels towards normal values and this improve the condition. Rasagiline was developed for the symptomatic treatment of Parkinson’s disease both as monotherapy in early disease and as adjunct therapy to levodopa + aminoacids decarboxylase inhibitor (LD + ADI) in patients with motor fluctuations. 2. Quality Introduction Drug Substance • Composition AZILECT contains rasagiline mesylate as the active substance. -
Colorimetric Approaches to Drug Analysis and Applications – a Review
REVIEW ARTICLE Am. J. PharmTech Res. 2019; 9(01) ISSN: 2249-3387 Journal home page: http://www.ajptr.com/ Colorimetric Approaches To Drug Analysis And Applications – A Review Sowjanya Gummadi*, Mohana Kommoju Department of Pharmaceutical Analysis, Institute of Pharmacy, GITAM (Deemed to be University), Visakhapatnam-530045, Andhra Pradesh, India ABSTRACT The main purpose of this review is to highlight the importance of colorimetric approaches to drug analysis both in dosage forms as well as biological samples. Colorimetric methods using colorimetric reagents are highly sensitive, specific and an easy way of determining various analytes in a variety of matrices within a short time. The colorimetric procedures discussed are statistically validated and reported in various quality control laboratories. Hence in the present review significance of colorimetric procedures, various reagents used along with principles and applications are mentioned. Key words: Colorimetric approaches, sensitive, matrices, quality control, applications. *Corresponding Author Email: [email protected] Received 01 November 2018, Accepted 23 December 2018 Please cite this article as: Gummadi S et al., Colorimetric Approaches To Drug Analysis And Applications – A Review. American Journal of PharmTech Research 2019. Gummadi et. al., Am. J. PharmTech Res. 2019; 9(01) ISSN: 2249-3387 INTRODUCTION Colorimetry is a technique which involves the quantitative estimation of colors frequently used in biochemical investigation. Color can be produced by any substance when it binds with color forming chromogens. The difference in color intensity results in difference in the absorption of light. The intensity of color is directly proportional to the concentration of the compound being measured.1 Wavelength between 380 nm to 780 nm forms the visible band of light in electromagnetic spectrum. -
Effects of Chronic Administration of Sibutramine on Body Weight, Food
Exp. Anim. 49(4), 239–249, 2000 Effects of Chronic Administration of Sibutramine on Body Weight, Food Intake and Motor Activity in Neonatally Monosodium Glutamate-Treated Obese Female Rats: Relationship of Antiobesity Effect with Monoamines Terutake NAKAGAWA1), Kiyoharu UKAI1), Tadashi OHYAMA1), Yutaka GOMITA2), and Hitoshi OKAMURA3) 1)Central Research Institute, Kaken Pharmaceutical Co. Ltd., 14 Shinomiya, Minamikawara-cho, Yamashina-ku, Kyoto 607-8042, 2)Department of Hospital Pharmacy, Okayama University Medical School, Shikada-cho 2–5–1, Okayama 700-8558, and 3)Department of Anatomy, Kobe University School of Medicine, 7–5–1 Chuohoku Kusunoki-cho, Kobe 650-0017, Japan Abstract: When the hypothalamic ventromedial nucleus and arcuate nucleus were destroyed in rats by treatment with monosodium glutamate in the neonatal stage, increase in the Lee index (body weight 1/3/body length) and in retroperitoneal fat as well as decreases in spontaneous motor activity, food consumption and growth hormone secretion function associated with hypothalamic low body length obesity (monosodium glutamate- treated obesity; MSG-OB) were observed as these rats grew. Treatment with sibutramine at 3 and 10 mg/kg p.o. once a day continuously for 14 days improved these parameters, and the degree of improvement was dose related. The plasma lipid values in MSG-OB rats, which were the same as those in normal rats, were decreased by consecutive administration of sibutramine. Levels of hypothalamic monoamines (MAs) such as norepinephrine, 5-HT (serotonin) and dopamine and their metabolites DOPAC, HVA and 5- HIAA were decreased in MSG-OB rats, and further decrease in them, though slight, was observed with consecutive daily administration of sibutramine, probably as a result of the feedback attributable to an increase in MA in synapses caused by inhibition of MA uptake by sibutramine. -
Experimental and Molecular Dynamics Simulation Studies of Partitioning and Transport Across Lipid Bilayer Membranes
University of Kentucky UKnowledge University of Kentucky Doctoral Dissertations Graduate School 2009 EXPERIMENTAL AND MOLECULAR DYNAMICS SIMULATION STUDIES OF PARTITIONING AND TRANSPORT ACROSS LIPID BILAYER MEMBRANES Ravindra Wadhumal Tejwani University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Tejwani, Ravindra Wadhumal, "EXPERIMENTAL AND MOLECULAR DYNAMICS SIMULATION STUDIES OF PARTITIONING AND TRANSPORT ACROSS LIPID BILAYER MEMBRANES" (2009). University of Kentucky Doctoral Dissertations. 738. https://uknowledge.uky.edu/gradschool_diss/738 This Dissertation is brought to you for free and open access by the Graduate School at UKnowledge. It has been accepted for inclusion in University of Kentucky Doctoral Dissertations by an authorized administrator of UKnowledge. For more information, please contact [email protected]. ABSTRACT OF DISSERTATION Ravindra Wadhumal Tejwani The Graduate School University of Kentucky 2009 EXPERIMENTAL AND MOLECULAR DYNAMICS SIMULATION STUDIES OF PARTITIONING AND TRANSPORT ACROSS LIPID BILAYER MEMBRANES ABSTRACT OF DISSERTATION A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the College of Pharmacy at the University of Kentucky By Ravindra Wadhumal Tejwani Lexington, Kentucky Director: Dr. Bradley D. Anderson, Professor of Pharmaceutical Sciences Lexington, Kentucky 2009 Copyright © Ravindra W. Tejwani 2009 ABSTRACT OF DISSERTATION EXPERIMENTAL AND MOLECULAR DYNAMICS SIMULATION STUDIES OF PARTITIONING AND TRANSPORT ACROSS LIPID BILAYER MEMBRANES Most drugs undergo passive transport during absorption and distribution in the body. It is desirable to predict passive permeation of future drug candidates in order to increase the productivity of the drug discovery process. -
Insights Into the Mechanisms of Action Ofthe MAO Inhibitors Phenelzine and Tranylcypromine
Insights into the Mechanisms of Action of the MAO Inhibitors Phenelzine and Tranylcypromine: A Review Glen B. Baker, Ph.D., Ronald T. Coutts, Ph.D., D.Sc., Kevin F. McKenna, M.D., and Rhonda L. Sherry-McKenna, B.Sc. Neurochemical Research Unit, Department of Psychiatry and Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta Submitted: July 10, 1992 Accepted: October 7, 1992 Although the non-selective monoamine oxidase inhibitors phenelzine and tranylcypromine have been used for many years, much still remains to be understood about their mechanisms of action. Other factors, in addition to the inhibition of monoamine oxidase and the subsequent elevation of brain levels of the catecholamines and 5-hydroxytryptamine, may contribute to the overall pharma- cological profiles ofthese drugs. This review also considers the effects on brain levels of amino acids and trace amines, uptake and release of neurotransmitter amines at nerve terminals, receptors for amino acids and amines, and enzymes other than monoamine oxidase, including enzymes involved in metabolism of other drugs. The possible contributions of metabolism and stereochemistry to the actions of these monoamine oxidase inhibitors are discussed. Key Words: amino acids, monoamine oxidase, neurotransmitter amines, phenelzine, tranylcypromine, uptake Despite the fact that the non-selective monoamine oxidase nerve endings (Baker et al 1977; Raiteri et al 1977) and/or (MAO) inhibitors phenelzine (PLZ) and tranylcypromine may act as neuromodulators through direct actions on recep- (TCP) (see Fig. 1) have been used clinically for many years, tors for the catecholamines and/or 5-HT (Jones 1983; much remains to be learned about theirmechanisms ofaction.