DRUG TREATMENTS for Parkinson's
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Novel Neuroprotective Compunds for Use in Parkinson's Disease
Novel neuroprotective compounds for use in Parkinson’s disease A thesis submitted to Kent State University in partial Fulfillment of the requirements for the Degree of Master of Science By Ahmed Shubbar December, 2013 Thesis written by Ahmed Shubbar B.S., University of Kufa, 2009 M.S., Kent State University, 2013 Approved by ______________________Werner Geldenhuys ____, Chair, Master’s Thesis Committee __________________________,Altaf Darvesh Member, Master’s Thesis Committee __________________________,Richard Carroll Member, Master’s Thesis Committee ___Eric_______________________ Mintz , Director, School of Biomedical Sciences ___Janis_______________________ Crowther , Dean, College of Arts and Sciences ii Table of Contents List of figures…………………………………………………………………………………..v List of tables……………………………………………………………………………………vi Acknowledgments.…………………………………………………………………………….vii Chapter 1: Introduction ..................................................................................... 1 1.1 Parkinson’s disease .............................................................................................. 1 1.2 Monoamine Oxidases ........................................................................................... 3 1.3 Monoamine Oxidase-B structure ........................................................................... 8 1.4 Structural differences between MAO-B and MAO-A .............................................13 1.5 Mechanism of oxidative deamination catalyzed by Monoamine Oxidases ............15 1 .6 Neuroprotective effects -
(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. -
Appendix A: Potentially Inappropriate Prescriptions (Pips) for Older People (Modified from ‘STOPP/START 2’ O’Mahony Et Al 2014)
Appendix A: Potentially Inappropriate Prescriptions (PIPs) for older people (modified from ‘STOPP/START 2’ O’Mahony et al 2014) Consider holding (or deprescribing - consult with patient): 1. Any drug prescribed without an evidence-based clinical indication 2. Any drug prescribed beyond the recommended duration, where well-defined 3. Any duplicate drug class (optimise monotherapy) Avoid hazardous combinations e.g.: 1. The Triple Whammy: NSAID + ACE/ARB + diuretic in all ≥ 65 year olds (NHS Scotland 2015) 2. Sick Day Rules drugs: Metformin or ACEi/ARB or a diuretic or NSAID in ≥ 65 year olds presenting with dehydration and/or acute kidney injury (AKI) (NHS Scotland 2015) 3. Anticholinergic Burden (ACB): Any additional medicine with anticholinergic properties when already on an Anticholinergic/antimuscarinic (listed overleaf) in > 65 year olds (risk of falls, increased anticholinergic toxicity: confusion, agitation, acute glaucoma, urinary retention, constipation). The following are known to contribute to the ACB: Amantadine Antidepressants, tricyclic: Amitriptyline, Clomipramine, Dosulepin, Doxepin, Imipramine, Nortriptyline, Trimipramine and SSRIs: Fluoxetine, Paroxetine Antihistamines, first generation (sedating): Clemastine, Chlorphenamine, Cyproheptadine, Diphenhydramine/-hydrinate, Hydroxyzine, Promethazine; also Cetirizine, Loratidine Antipsychotics: especially Clozapine, Fluphenazine, Haloperidol, Olanzepine, and phenothiazines e.g. Prochlorperazine, Trifluoperazine Baclofen Carbamazepine Disopyramide Loperamide Oxcarbazepine Pethidine -
PSP: Some Answers
PSP: Some Answers Lawrence I. Golbe, MD Professor of Neurology, Rutgers Robert Wood Johnson Medical School Director of Clinical Affairs and Scientific Advisory Board Chairman, CurePSP October 2017 What is Progressive Supranuclear Palsy (PSP)? Of the approximately five to seven of every 100,000 people in Canada with progressive supranuclear palsy (PSP), few, if any, had ever heard of the disease before their diagnosis. In fact, most patients with PSP report that their family doctors knew nothing about it until a neurologist made the diagnosis. As of now, three of every four people with a diagnosis of PSP could have been diagnosed earlier, if their doctor had suspected it and performed the appropriate examination. However, it is appearing in medical journals more and more often, which will help doctors become familiar with PSP. This pamphlet should help patients and their families do the same. Why has no one heard of PSP? PSP is rare: no one even realized it existed until 1963, when several patients were first described at a national neurology research convention and the disease was given its name. In retrospect, at least 12 cases of PSP had appeared in the medical literature between 1909 and 1962, but because of its resemblance to Parkinson’s, it wasn’t recognized as a distinct disease. The brain under the microscope is almost identical to that of “post-encephalitic parkinsonism,” a common condition in the early 20th century but now nearly extinct, which also made for erroneous diagnoses during that era. Although PSP is slightly more common than the well-known amyotrophic lateral sclerosis (called ALS, or Lou Gehrig’s disease in the U.S. -
Apo-Ropinirole
New Zealand Data Sheet APO-ROPINIROLE 1. PRODUCT NAME APO-ROPINIROLE 0.25mg, 0.5mg, 1mg, 2mg, 3mg, 4mg and 5mg tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Ropinirole hydrochloride 0.25mg Ropinirole hydrochloride 0.5mg Ropinirole hydrochloride 1mg Ropinirole hydrochloride 2mg Ropinirole hydrochloride 3mg Ropinirole hydrochloride 4mg Ropinirole hydrochloride 5mg Excipient(s) with known effect Contains lactose. For the full list of excipients, see section 6.1 3. PHARMACEUTICAL FORM APO-ROPINIROLE is available as oral, film coated tablets in the following strengths: APO-ROPINIROLE 0.25mg tablets are white, pentagonal, biconvex film-coated tablet identified by an engraved “ROP” over “.25” on one side and “APO’ on the other side. Each tablet typically weighs about 153mg. APO-ROPINIROLE 0.5mg tablets are yellow, pentagonal, biconvex film-coated tablet identified by an engraved “ROP” over “.5” on one side and “APO’ on the other side. Each tablet typically weighs about 153mg. APO-ROPINIROLE 1mg tablets are green, pentagonal, biconvex film-coated tablet identified by an engraved “ROP” over “1” on one side and “APO’ on the other side. Each tablet typically weighs about 153mg. APO-ROPINIROLE 2mg tablets are pink, pentagonal, biconvex film-coated tablet identified by an engraved “ROP” over “2” on one side and “APO’ on the other side. Each tablet typically weighs about 153mg. APO-ROPINIROLE 3mg tablets are purple, pentagonal, biconvex film-coated tablet identified by an engraved “ROP” over “3” on one side and “APO’ on the other side. Each tablet typically weighs about 153mg. APO-ROPINIROLE 4mg tablets are pale brown, pentagonal, biconvex film-coated tablet identified by an engraved “ROP” over “4” on one side and “APO’ on the other side. -
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. -
Compositions for Continuous Administration of Dopa
(19) TZZ ¥ _T (11) EP 2 432 454 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 9/08 (2006.01) A61K 9/10 (2006.01) 01.03.2017 Bulletin 2017/09 A61K 31/198 (2006.01) A61P 25/16 (2006.01) (21) Application number: 10725880.8 (86) International application number: PCT/IL2010/000400 (22) Date of filing: 17.05.2010 (87) International publication number: WO 2010/134074 (25.11.2010 Gazette 2010/47) (54) COMPOSITIONS FOR CONTINUOUS ADMINISTRATION OF DOPA DECARBOXYLASE INHIBITORS ZUSAMMENSETZUNGEN FÜR DIE KONTINUIERLICHE VERABREICHUNG VON DOPA-DECARBOXYLASEHEMMERN COMPOSITIONS POUR ADMINISTRATION CONTINUE D’UN INHIBITEUR DE LA DOPA-DÉCARBOXYLASE (84) Designated Contracting States: (74) Representative: ABG Patentes, S.L. et al AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Avenida de Burgos, 16D GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO Edificio Euromor PL PT RO SE SI SK SM TR 28036 Madrid (ES) (30) Priority: 19.05.2009 US 179511 P (56) References cited: WO-A1-2006/006929 US-A- 4 409 233 (43) Date of publication of application: 28.03.2012 Bulletin 2012/13 • NYHOLM D: "Enteral levodopa/carbidopa gel infusion for the treatment of motor fluctuations (73) Proprietor: Neuroderm Ltd and dyskinesias in advanced Parkinson’s 74036 Ness Ziona (IL) disease" EXPERT REVIEW OF NEUROTHERAPEUTICS, FUTURE DRUGS, (72) Inventors: LONDON, GB LNKD- • YACOBY-ZEEVI, Oron DOI:10.1586/14737175.6.10.1403, vol. 6, no. 10, 1 60946 Bitsaron (IL) January 2006 (2006-01-01), pages 1403-1411, •NEMAS,Mara XP008082627 ISSN: 1473-7175 70700 Gedera (IL) Remarks: Thefile contains technical information submitted after the application was filed and not included in this specification Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. -
Oral Systemic Therapy Pharmacy Toolkit
Oral Systemic Therapy Pharmacy Toolkit PROCARBAZINE INSTRUCTIONS FOR THE PHARMACIST Prescription • All orders should be written on a pre-printed order; if not, compare prescription to standard regimens in the Systemic Therapy Manual to confirm the dosing and instructions o The order must be signed by BOTH the prescriber (at the bottom) AND at least one other oncology health professional (nurse or hospital pharmacist) who has verified the order o Measure the patient’s height (cm) and weight (Kg), then recalculate body surface area (BSA) • The prescription may not be refilled (unless specifically ordered by the oncologist) and it may not be filled as a continuing care prescription o If the prescriber has written for refills, do not dispense until the oncology team authorizes the refill; Blood work must be checked for each cycle. • Always check for drug-drug interactions, especially before the first cycle, as described below. Consult the Drug Interactions section (page 4), and consider an online drug interactions checking program. • Check with patient for any other medications filled at a different pharmacy Handling and Dispensing • When handling this drug, disposable gloves should be worn at all times by any woman of child-bearing potential. Counting trays and other equipment directly exposed to the drug should be cleaned with a sodium hypochlorite (bleach) solution (or soap and water), followed by rinsing with copious amounts of water (wear gloves). Do not open capsules in an open air environment and risk inhalation of powder. • ALWAYS affix the auxiliary label to identify this medication as “Cancer Chemotherapy”- this is an important warning label for other health professionals caring for the patient. -
Neuroenhancement in Healthy Adults, Part I: Pharmaceutical
l Rese ca arc ni h li & C f B o i o l e Journal of a t h n Fond et al., J Clinic Res Bioeth 2015, 6:2 r i c u s o J DOI: 10.4172/2155-9627.1000213 ISSN: 2155-9627 Clinical Research & Bioethics Review Article Open Access Neuroenhancement in Healthy Adults, Part I: Pharmaceutical Cognitive Enhancement: A Systematic Review Fond G1,2*, Micoulaud-Franchi JA3, Macgregor A2, Richieri R3,4, Miot S5,6, Lopez R2, Abbar M7, Lancon C3 and Repantis D8 1Université Paris Est-Créteil, Psychiatry and Addiction Pole University Hospitals Henri Mondor, Inserm U955, Eq 15 Psychiatric Genetics, DHU Pe-psy, FondaMental Foundation, Scientific Cooperation Foundation Mental Health, National Network of Schizophrenia Expert Centers, F-94000, France 2Inserm 1061, University Psychiatry Service, University of Montpellier 1, CHU Montpellier F-34000, France 3POLE Academic Psychiatry, CHU Sainte-Marguerite, F-13274 Marseille, Cedex 09, France 4 Public Health Laboratory, Faculty of Medicine, EA 3279, F-13385 Marseille, Cedex 05, France 5Inserm U1061, Idiopathic Hypersomnia Narcolepsy National Reference Centre, Unit of sleep disorders, University of Montpellier 1, CHU Montpellier F-34000, Paris, France 6Inserm U952, CNRS UMR 7224, Pierre and Marie Curie University, F-75000, Paris, France 7CHU Carémeau, University of Nîmes, Nîmes, F-31000, France 8Department of Psychiatry, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany *Corresponding author: Dr. Guillaume Fond, Pole de Psychiatrie, Hôpital A. Chenevier, 40 rue de Mesly, Créteil F-94010, France, Tel: (33)178682372; Fax: (33)178682381; E-mail: [email protected] Received date: January 06, 2015, Accepted date: February 23, 2015, Published date: February 28, 2015 Copyright: © 2015 Fond G, et al. -
Pramipexole V2.1 Last Reviewed: 22/04/2021 Review Date: 22/04/2024
Pramipexole V2.1 Last reviewed: 22/04/2021 Review date: 22/04/2024 Pramipexole Traffic light classification- Amber 2 Information sheet for Primary Care Prescribers CLINICAL INFORMATION Key points/interactions Nausea is a common early side effect but usually responds to domperidone (10mg tds, or lowest effective dose – see MHRA advice) Ropinirole MR is first line dopamine agonist. Pramipexole MR should be reserved for patients in whom this is not suitable- see formulary. Dopamine agonists may cause compulsive/addictive behaviours such as gambling, compulsive shopping and hyper sexuality. Patients rarely recognise such changes as side effects and rarely report them unless specifically asked. Licensed Indications Treatment of idiopathic Parkinson's disease. Pramipexole may be used alone (without levodopa) or in combination with levodopa throughout the disease, through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occur (end of dose or “on-off” fluctuations). Therapeutic Summary As per the licensed indication. NICE recommendations for the use of Pramipexole in Parkinson’s disease are: Consider a choice of dopamine agonists, levodopa or monoamine oxidase B (MAO-B) inhibitors for people in the early stages of Parkinson's disease whose motor symptoms do not impact their quality of life. Do not offer ergot-derived dopamine agonists as first-line treatment for Parkinson's disease. Offer a choice of dopamine agonists, MAO-B inhibitors or catechol-O-methyltransferase (COMT) -
Integrated Approaches for Genome-Wide Interrogation of The
MINIREVIEW THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 290, NO. 32, pp. 19471–19477, August 7, 2015 © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A. 5-HT serotonin receptor agonism have long been docu- Integrated Approaches for 2B mented to induce severe, life-threatening valvular heart disease Genome-wide Interrogation of (6–8). Indeed, based on the potent 5-HT2B agonist activity of the Druggable Non-olfactory G certain ergot derivatives used in treating Parkinson disease and migraine headaches (e.g. pergolide, cabergoline, and dihydroer- Protein-coupled Receptor gotamine), we correctly predicted that these medications * would also induce valvular heart disease (7, 8). Two of these Superfamily drugs (pergolide and cabergoline) were withdrawn from the Published, JBC Papers in Press, June 22, 2015, DOI 10.1074/jbc.R115.654764 Bryan L. Roth1 and Wesley K. Kroeze international market following large-scale trials demonstrating From the Department of Pharmacology, University of North Carolina their life-threating side effects (8, 9). In follow-up studies, we Chapel Hill School of Medicine, Chapel Hill, North Carolina 27514 surveyed 2200 FDA-approved and investigational medications, finding that 27 had potentially significant 5-HT2B agonism, of G-protein-coupled receptors (GPCRs) are frequent and fruit- which 6 are currently FDA-approved (guanfacine, quinidine, ful targets for drug discovery and development, as well as being xylometazoline, oxymetazoline, fenoldopam, and ropinirole) off-targets for the side effects of a variety of medications. Much (10). Interestingly, of the 2200 drugs screened, around 30% dis- of the druggable non-olfactory human GPCR-ome remains played significant 5-HT2B antagonist activity (10), indicating under-interrogated, and we present here various approaches that 5-HT2B receptors represent a “promiscuous target” for that we and others have used to shine light into these previously approved and candidate medications. -
Neuronal Dopamine D3 Receptors: Translational Implications for Preclinical Research and CNS Disorders
biomolecules Review Neuronal Dopamine D3 Receptors: Translational Implications for Preclinical Research and CNS Disorders Béla Kiss 1, István Laszlovszky 2, Balázs Krámos 3, András Visegrády 1, Amrita Bobok 1, György Lévay 1, Balázs Lendvai 1 and Viktor Román 1,* 1 Pharmacological and Drug Safety Research, Gedeon Richter Plc., 1103 Budapest, Hungary; [email protected] (B.K.); [email protected] (A.V.); [email protected] (A.B.); [email protected] (G.L.); [email protected] (B.L.) 2 Medical Division, Gedeon Richter Plc., 1103 Budapest, Hungary; [email protected] 3 Spectroscopic Research Department, Gedeon Richter Plc., 1103 Budapest, Hungary; [email protected] * Correspondence: [email protected]; Tel.: +36-1-432-6131; Fax: +36-1-889-8400 Abstract: Dopamine (DA), as one of the major neurotransmitters in the central nervous system (CNS) and periphery, exerts its actions through five types of receptors which belong to two major subfamilies such as D1-like (i.e., D1 and D5 receptors) and D2-like (i.e., D2, D3 and D4) receptors. Dopamine D3 receptor (D3R) was cloned 30 years ago, and its distribution in the CNS and in the periphery, molecular structure, cellular signaling mechanisms have been largely explored. Involvement of D3Rs has been recognized in several CNS functions such as movement control, cognition, learning, reward, emotional regulation and social behavior. D3Rs have become a promising target of drug research and great efforts have been made to obtain high affinity ligands (selective agonists, partial agonists and antagonists) in order to elucidate D3R functions. There has been a strong drive behind the efforts to find drug-like compounds with high affinity and selectivity and various functionality for D3Rs in the hope that they would have potential treatment options in CNS diseases such as schizophrenia, drug abuse, Parkinson’s disease, depression, and restless leg syndrome.