(12) Patent Application Publication (10) Pub. No.: US 2013/0253056A1 Nemas Et Al
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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 -
Therapy for Movement Disorders
Cynthia Comella, MD, FAAN Rush University Medical Center Chicago, IL TREATMENT OF MOTOR SYMPTOMS IN PARKINSON DISEASE Disclosures . Compensation/honoraria for services as a consultant or an advisory committee member: Acadia, Aeon, Allergan, Inc; Impax Pharmaceuticals; Ipsen Biopharmaceuticals, Inc; Medtronic Inc.; Merz Pharmaceuticals; Neurocrine. Royalties: Cambridge, Humana Press; Wolters Kluwer Objectives Treatment of PD . Available treatments for motor PD Treatment of motor symptoms Treatment of motor complications Motor fluctuations Dyskinesia . Overview new therapies in clinical trial Not my objectives Before I came here I was confused about this subject. Having listened to your lecture I am still confused. But on a higher level. Enrico Fermi PD motor symptoms: Therapeutic targets Oertel W, Shulz JB. J Neurochem 2016 . No effective neuroprotective agent . Monotherapy (Efficacious) Levodopa Dopamine agonists: (pramipexole, ropinirole, rotigotine) MAO-B inhibitors: (selegiline, rasagiline) Amantadine (likely) . Motor fluctuations (Efficacious) Efficacious: Dopamine agonists (pramipexole, ropinirole, rotigotine, apomorphine) Levodopa gel intestinal infusions COMT inhibitors (entacapone, tolcapone, opicapone) MAO-B inhibitors (rasagiline, safinamide) Zonisamide Bilateral STN and GPi stimulation . Dyskinesia (Efficacious) Intestinal infusions Amantadine Bilateral STN and GPi stimulation clozapine Fox et al. Mov Disord March 2018 Modest benefit . MAO-B inhibitors (selegiline, rasagiline, safinamide) Modest benefit -
Screening of a Composite Library of Clinically Used Drugs and Well
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Pharmacol Manuscript Author Res. Author Manuscript Author manuscript; available in PMC 2017 November 01. Published in final edited form as: Pharmacol Res. 2016 November ; 113(Pt A): 18–37. doi:10.1016/j.phrs.2016.08.016. Screening of a composite library of clinically used drugs and well-characterized pharmacological compounds for cystathionine β-synthase inhibition identifies benserazide as a drug potentially suitable for repurposing for the experimental therapy of colon cancer Nadiya Druzhynaa, Bartosz Szczesnya, Gabor Olaha, Katalin Módisa,b, Antonia Asimakopoulouc,d, Athanasia Pavlidoue, Petra Szoleczkya, Domokos Geröa, Kazunori Yanagia, Gabor Töröa, Isabel López-Garcíaa, Vassilios Myrianthopoulose, Emmanuel Mikrose, John R. Zatarainb, Celia Chaob, Andreas Papapetropoulosd,e, Mark R. Hellmichb,f, and Csaba Szaboa,f,* aDepartment of Anesthesiology, The University of Texas Medical Branch, Galveston, TX, USA bDepartment of Surgery, The University of Texas Medical Branch, Galveston, TX, USA cLaboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Greece dCenter of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens, Greece eNational and Kapodistrian University of Athens, School of Pharmacy, Athens, Greece fCBS Therapeutics Inc., Galveston, TX, USA Abstract Cystathionine-β-synthase (CBS) has been recently identified as a drug target for several forms of cancer. Currently no -
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). -
Gait Analysis in Advanced Parkinson's Disease – Effect of Levodopa And
ORIGINAL ARTICLE Gait Analysis in Advanced Parkinson’s Disease – Effect of Levodopa and Tolcapone Din-E Shan, Shwn-Jen Lee, Ling-Yi Chao, and Shyh-Ing Yeh ABSTRACT: Objective: To determine the therapeutic effect of levodopa/benserazide and tolcapone on gait in patients with advanced Parkinson’s disease. Methods: Instrumental gait analysis was performed in 38 out of 40 patients with wearing-off phenomenon during a randomized, double-blind, placebo- controlled trial of tolcapone. R e s u l t s : Gait analysis disclosed a significant improvement by levodopa/benserazide in walking speed, stride length and the range of motion of hip, knee and ankle joints. At the end of the study, both the UPDRS motor scores during off-period and the percentage of off time improved significantly using tolcapone. However, gait analysis could not confirm this improvement. With respect to levodopa/benserazide effect, the reduction in rigidity correlated with improved angular excursion of the ankle, whereas the decreased bradykinesia correlated with improved stride length and angular excursion of the hip and knee joints. Conclusion: The results of our gait analysis confirmed that in parkinsonian patients with fluctuating motor symptoms levodopa/benserazide, but not tolcapone, produced a substantial improvement. RÉSUMÉ: Analyse de la démarche chez les patients en phase avancée de la maladie de Parkinson – Effet de la lévodopa et du tolcapone. Objectif: Le but de cette étude était de déterminer l’effet thérapeutique de la lévodopa/bensérazide et du tolcapone sur la démarche, chez les patients en phase avancée de la maladie de Parkinson. Méthodes: Une analyse instrumentale de la démarche a été réalisée chez 38 de 40 patients ayant un phénomène de détérioration de fin de dose pendant un essai randomisé, en double insu, contrôlé par placebo, du tolcapone. -
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. -
Carbidopa and Levodopa | Memorial Sloan Kettering Cancer Center
PATIENT & CAREGIVER EDUCATION Carbidopa and Levodopa This information from Lexicomp® explains what you need to know about this medication, including what it’s used for, how to take it, its side effects, and when to call your healthcare provider. Brand Names: US Duopa; Rytary; Sinemet; Sinemet CR [DSC] Brand Names: Canada AA-Levocarb CR; APO-Levocarb; APO-Levocarb 100/25; APO-Levocarb 250/25; DOM-Levo-Carbidopa; Duodopa; MINT-Levocarb; PMS-Levocarb CR; Pro-Lecarb; PRO-Levocarb-100/25 [DSC]; Sinemet 100/25; Sinemet 250/25; Sinemet CR 200/50 [DSC]; Sinemet CR [DSC]; TEVA-Levocarbidopa What is this drug used for? It is used to treat Parkinson’s disease. It is used to treat signs like Parkinson’s disease caused by other health problems. It may be given to you for other reasons. Talk with the doctor. What do I need to tell my doctor BEFORE I take this drug? If you are allergic to this drug; any part of this drug; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had. If you have any of these health problems: Glaucoma, a skin lump or growth, or a history of skin cancer. Carbidopa and Levodopa 1/10 If you are taking any of these drugs: Reserpine or tetrabenazine. If you are taking any of these drugs: Linezolid or methylene blue. If you have taken certain drugs for depression or Parkinson’s disease in the last 14 days. This includes isocarboxazid, phenelzine, tranylcypromine, selegiline, or rasagiline. Very high blood pressure may happen. -
Summary of Drug Limitations Mary C
RON DESANTIS GOVERNOR SUMMARY OF DRUG LIMITATIONS MARY C. MAYHEW SECRETARY **Medications listed in this document may or may not require a prior authorization. Please view the Preferred Drug List at: http://ahca.myflorida.com/Medicaid/Prescribed_Drug/pharm_thera/fmpdl.shtml** Summary of Drug Limitations Abilify (aripiprazole) 2mg, 5mg, 20mg, 30mg tablets Minimum age = 6; Maximum of 1 tablet per day Abilify (aripiprazole) 10mg, 15mg tablets Minimum age = 6; Maximum of 15mg per day for ages = 6 - 11; Maximum of 30mg per day for ages = 12-17 Maximum of 1 tablet per day Abilify (aripiprazole) Discmelt 10mg, 15mg tabs Minimum age = 6; Maximum of 15mg per day for ages = 6 - 11; Maximum of 30mg per day for ages = 12-17; Maximum of 2 tablets per day Abilify (aripiprazole) 1mg/ml solution Minimum age = 6; Maximum of 15ml per day for ages = 6 - 11; Maximum of 30ml per day for ages = 12-17; Maximum of 30ml per day for ages =/> 18 Abilify Maintena (aripiprazole) syringe/vial Minimum age = 18; Maximum of 1 syringe or vial every 28 days Absorica (isotretinoin) 10mg, 20mg, 25mg,30mg, 35mg, & Minimum age = 12 40mg capsules Abstral (fentanyl citrate) sublingual tablets Minimum age = 18; Maximum of 4 sublingual tablets per day Acanya (benzoyl peroxide/clindamycin)Gel, gel pump Minimum Age= 12 Accolate (zafirlukast) tablets Maximum of 3 tablets per day Aciphex (rabeprazole) 5mg, 10mg sprinkle capsules Minimum age = 1; Maximum age = 11; Maximum of 1 capsule per day Aciphex (rabeprazole) 20mg tablets Minimum age = 1; Maximum of 2 tablets per day Actemra (tocilizumab) 80mg/4ml, 200mg/10ml, Minimum age= 2 400mg/20ml Vials, & 162mg/0.9ml Syringe Actimmune (Interferon Gamma-1b) Maximum of 6ml every 28days Actiq (fentanyl citrate) Lozenges Minimum age = 18; Maximum of 4 lozenges per day Activella (estradiol/norethindrone) tablets Minimum age = 18 Updated 02/28/2019 1 RON DESANTIS GOVERNOR SUMMARY OF DRUG LIMITATIONS MARY C. -
210913Orig1s000 CLINICAL PHARMACOLOGY REVIEW(S)
CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 210913Orig1s000 CLINICAL PHARMACOLOGY REVIEW(S) Office of Clinical Pharmacology Review NDA Number 212489 Link to EDR \\cdsesub1\evsprod\nda212489 Submission Date 04/26/2019 Submission Type 505(b)(1) NME NDA (Standard Review) Brand Name ONGENTYS Generic Name opicapone Dosage Form/Strength and Capsules: 25 mg and 50 mg Dosing Regimen 50 mg administered orally once daily at bedtime Route of Administration Oral Proposed Indication Adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s Disease experiencing “OFF” episodes Applicant Neurocrine Biosciences, Inc. (NBI) Associated IND IND (b) (4) OCP Review Team Mariam Ahmed, Ph.D. Atul Bhattaram, Ph.D. Sreedharan Sabarinath, Ph.D. OCP Final Signatory Mehul Mehta, Ph.D. 1 Reference ID: 4585182 Table of Contents 1. EXECUTIVE SUMMARY .............................................................................................................................................................. 4 1.1 Recommendations ..................................................................................................................................................... 4 1.2 Post-Marketing Requirements and Commitments ......................................................................................... 6 2. SUMMARY OF CLINICAL PHARMACOLOGY ASSESSMENT ............................................................................................. 6 2.1 Pharmacology and Clinical Pharmacokinetics .................................................................................................. -
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.