Insomnia and It's Management
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Neuroscience Product Handbook
www.MedChemExpress.com MedChemExpressMedChemExpress Neuroscience Product Handbook Pain Biological Rhythms and Sleep Neuromuscular Diseases AutonomicNeuroendocrine Somatosensation metabolism Regulation Processes transduction Behavioral Neuroethology Neuroendocrin feature soding Food Intake oral and speech From the itineraries of and Energy Balance vocal/social 8,329 attendees Touch Thirst and communication Water Balance social behavior Development peptides at the 2018 SfN meeting Ion Channels and Evolution Stress and social cognition opiates the Brain monoamines Spinal Cord Adolescent Development PTSD Injury and Plasticity Postnatal autism Developmental fear Neurogenesis Disorders human social Mood cognition ADHD, Disorders Human dystexia Anxiety Cognition and Neurogenesis depression Appetitive Behavior and Gllogenesis bipolar and Aversive timing Development of Motor, Schizophrenia Learning perception Sensory,and Limbic Systems perceptual learning Other Psychiatric executive attention Stem Cells... mitochondria Emotionfunction human Parkinson's Glial Mechanisms biomarkers reinforcement long-term Disease Synaptogenesis human human memory Huntington's Transplant and ... Development Neurotransm., Motivation decisions working and Regen Axon and Transportors, memory PNS G-Protein...Signaling animal Dendrite reward decision visual Other Movement Development Receptors learning and memory model microglia making decisions Disorders Demyelinating NMDA dopamine ataxia Disorders place cells, GABA, LT P Synaptic grid cells gly... Plasticity striatum -
Sleep Disorders & Medicine
Nava Zisapel et al., J Sleep Disord Ther 2015, 4:4 http://dx.doi.org/10.4172/2167-0277.S1.002 Annual Summit on Sleep Disorders & Medicine August 10-12, 2015 San Francisco, USA Piromelatine: A novel melatonin-serotonin agonist for the treatment of insomnia disorder and neurocognitive comorbidities Nava Zisapel1 and Moshe Laudon2 1Tel Aviv University, Israel 2Neurim Pharmaceuticals Ltd., Israel nsomnia affects 30%-50% of the general population and even more so (63%) among patients with mild cognitive impairments I(MCI). Alzheimer’s disease (AD) risk among insomnia patients is approximately 3 fold that of good sleepers. Furthermore, poor sleep quality is associated with faster cognitive decline and may be an early marker of cognitive decline in mid life. Improvement of sleep may be critically important for maintaining or enhancing cognitive function in patients with MCI or AD. Current hypnotic medications (benzodiazepines and benzodiazepines-like) are associated with cognitive and memory impairments, increased risk of falls, accidents and dependency. Melatonin receptors agonists are safe and effective drugs for primary insomnia and circadian rhythm sleep disorders and are potentially useful for cognition and sleep in. Piromelatine is a novel investigational MT1\MT2 and 5HT1A\D receptors agonist developed for primary and co-morbid insomnia. In Phase-I studies it demonstrated good oral bioavailability (Elimination half-life 2.8±1.4 hours), good safety & tolerability profile across a wide dose range and provided the first indication for beneficial effects on sleep maintenance. In a Phase-II study in insomnia patients, piromelatine demonstrated significant improvements in sleep maintenance based on objective assessments (polysomnography recorded wake after sleep onset, sleep efficiency and total sleep time) and good safety profile with no detrimental effects on next-day psychomotor performance and memory. -
TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub
US 20200187851A1TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No .: US 2020/0187851 A1 Offenbacher et al. (43 ) Pub . Date : Jun . 18 , 2020 ( 54 ) PERIODONTAL DISEASE STRATIFICATION (52 ) U.S. CI. AND USES THEREOF CPC A61B 5/4552 (2013.01 ) ; G16H 20/10 ( 71) Applicant: The University of North Carolina at ( 2018.01) ; A61B 5/7275 ( 2013.01) ; A61B Chapel Hill , Chapel Hill , NC (US ) 5/7264 ( 2013.01 ) ( 72 ) Inventors: Steven Offenbacher, Chapel Hill , NC (US ) ; Thiago Morelli , Durham , NC ( 57 ) ABSTRACT (US ) ; Kevin Lee Moss, Graham , NC ( US ) ; James Douglas Beck , Chapel Described herein are methods of classifying periodontal Hill , NC (US ) patients and individual teeth . For example , disclosed is a method of diagnosing periodontal disease and / or risk of ( 21) Appl. No .: 16 /713,874 tooth loss in a subject that involves classifying teeth into one of 7 classes of periodontal disease. The method can include ( 22 ) Filed : Dec. 13 , 2019 the step of performing a dental examination on a patient and Related U.S. Application Data determining a periodontal profile class ( PPC ) . The method can further include the step of determining for each tooth a ( 60 ) Provisional application No.62 / 780,675 , filed on Dec. Tooth Profile Class ( TPC ) . The PPC and TPC can be used 17 , 2018 together to generate a composite risk score for an individual, which is referred to herein as the Index of Periodontal Risk Publication Classification ( IPR ) . In some embodiments , each stage of the disclosed (51 ) Int. Cl. PPC system is characterized by unique single nucleotide A61B 5/00 ( 2006.01 ) polymorphisms (SNPs ) associated with unique pathways , G16H 20/10 ( 2006.01 ) identifying unique druggable targets for each stage . -
Melatonin Receptor Agonist Piromelatine Ameliorates Impaired Glucose Metabolism in Chronically Stressed Rats Fed a High-Fat Diet
1521-0103/364/1/55–69$25.00 https://doi.org/10.1124/jpet.117.243998 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 364:55–69, January 2018 Copyright ª 2017 by The American Society for Pharmacology and Experimental Therapeutics Melatonin Receptor Agonist Piromelatine Ameliorates Impaired Glucose Metabolism in Chronically Stressed Rats Fed a High-Fat Diet Jun Zhou, Deng Wang, XiaoHong Luo, Xu Jia, MaoXing Li, Moshe Laudon, RuXue Zhang, and ZhengPing Jia College of Pharmacy, Lanzhou University, Lanzhou, PR China (J.Z., M.X.L, R.X.Z, Z.P.J.); Xi’an Daxing Hospital, Shaanxi, PR China (D.W.); Lanzhou General Hospital of PLA, Lanzhou, PR China (J.Z., X.L., M.X.L, R.X.Z, Z.P.J.); Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China (X.J.); and Drug Discovery, Neurim Pharmaceuticals Ltd., Tel-Aviv, Israel (M.L.) Downloaded from Received July 19, 2017; accepted October 6, 2017 ABSTRACT Modern lifestyle factors (high-caloric food rich in fat) and daily combined with CS (CF). The results showed that piromelatine chronic stress are important risk factors for metabolic distur- prevented the suppression of body weight gain and energy jpet.aspetjournals.org bances. Increased hypothalamic-pituitary-adrenal (HPA) axis intake induced by CF and normalized CF-induced hyperglycemia activity and the subsequent excess production of glucocorticoids and homeostasis model assessment–IR index, which suggests (GCs) in response to chronic stress (CS) leads to increases in that piromelatine prevented whole-body IR. Piromelatine also metabolic complications, such as type 2 diabetes and insulin prevented CF-induced dysregulation of genes involved in resistance (IR). -
Programa Cooperación Farma-Biotech 8º Encuentro (7 De Mayo De 2013)
Programa Cooperación Farma-Biotech 8º encuentro (7 de mayo de 2013) Lorediplon: “best-in-class” product for insomnia treatment Madrid,,y 7 de mayo de 2013 Programa Cooperación Farma-Biotech 8º encuentro (7 de mayo de 2013) Content 1. The Company 2. The Product a) Target Indications b) Innovative mechanisms of action c) Differential features facing the market d) Current status of development e) IPR protect io n f) Pitfalls & Risks to be considered 3. Partnering Opportunities Programa Cooperación Farma-Biotech 8º encuentro (7 de mayo de 2013) The Company Who we are IItnternati onal pri vat tlely-hhldheld pharmaceu tiltical company Founded in 1959 Mission Business areas To advance the wellbeinggy of society Pharmaceuticals OTCs & personal health Diagnostics Worldwide operations Fine chemicals Headquarter in Barcelona Food & feed additives Presence in 93 countries Programa Cooperación Farma-Biotech 8º encuentro (7 de mayo de 2013) The Company Total turnover 2012 €819 million (+2% vs 2011) International turnover €365 million (44% of total) Total staff 2012 2,201 (abroad 593) Inves tmen t in R&D 12. 1% ofitilf prescription sales Given the maximum rating by the Spanish national pharma assessment system (Profarma) Programa Cooperación Farma-Biotech 8º encuentro (7 de mayo de 2013) The Product - Target Indication Insomnia In 2010, there were 53 million prevalent cases of insomnia in the 7 MM (US, Japan, France, Germany, Italy, Spain, and UK). US (25.7 million), Japan (8.2 million), France (6.8 million), Germany and Italy (3.5 million), Spain and -
Diapositiva 1
New treatment options for sleep disorders Chairs: Gabriella Gobbi and Anton Y. Bespalov . Novel selective melatonin MT2 receptor agonist in the treatment of insomnia . Gabriella Gobbi, Canada . Orexin receptor antagonists and insomnia treatment: state of the art . Anthony Gotter, US . Development of piromelatine, a novel multimodal sleep medicine . Nava Zisapel, Israel . The brain H3-receptor as a novel therapeutic target for vigilance and sleep-wake disorders Abstract . Jian Sheng Lin , France Prevalence insomnia in Canada and Europe Canadian survey1 European survey2 on sleep and related factors on insomnia and sleep symptoms (N=2000) (N=25,579) 50 50 40.4% 40 40 34.5% 30 30 Respondents (%) Respondents (%) 20 20 13.4% 9.8% 10 10 0 0 Insomnia symptoms Insomnia disorder Insomnia symptoms Insomnia disorder 1. Morin et al. Can J Psychiatry. 2011;56:540-548; 2. Ohayon et al. Sleep Med. 2009;10:952-960. Prevalence in the American Insomnia Survey . 10,094 members of a managed health care plan . Prevalence 23.6%* . Insomnia symptoms: about 45% . Risk of insomnia higher in: . Women vs men . Older age vs younger groups (18-64 vs >65 y) . Disabled or retired vs employed . Shift workers vs day workers . Obese vs normal BMI Diagnosis based on any one of 3 systems: DSM-IV-TR, ICD-10, RDC/ICSD-2. *Insomnia assessed using Brief Insomnia Questionnaire (BIQ). Roth et al. Biol Psychiatry. 2011;69:592-600. Insomnia and Societal Burden •Increased risks of depression and alcohol Psychiatric dependence1,2 •Increased risks of hypertension, metabolic Health syndrome, and coronary heart disease2 •Decreased productivity and increased Occupational absenteeism1,2 Economic •Increased health care costs1,2 Public safety •Increased risks of accidents1 1. -
Blood Pressure Reducing Effects of Piromelatine and Melatonin in Spontaneously Hypertensive Rats
Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2013; 17: 2449-2456 Blood pressure reducing effects of piromelatine and melatonin in spontaneously hypertensive rats L. HUANG 1,2 , C. ZHANG 1, Y. HOU 1, M. LAUDON 4, M. SHE 3, S. YANG 3, L. DING 3, H. WANG 2, Z. WANG 5, P. HE 1, W. YIN 1,3 1Institute of Cardiovascular Research, Key Laboratory for Arteriosclerosis of Hunan Province, University of South China, Hengyang, Hunan, People's Republic of China, China 2Department of Operative Surgery, University of South China, Hengyang, Hunan, People's Republic of China, China 3Department of Biochemistry and Molecular Biology, School of Life Sciences and Technology, University of South China, Hengyang, Hunan, People's Republic of China, China 4Drug discovery, Neurim Pharmaceuticals Ltd, Tel-Aviv, Israel 5Department of Laboratory Animal Science, University of South China, Hengyang, Hunan, People's Republic of China, China Abstract. – BACKGROUND : Recently, wide - Key Words: spread interest has grown regarding melatonin Piromelatine, Melatonin, Hypertension, Sponta - treatment of hypertension including its cardiopro - neously hypertensive rats, Metabolic diseases. tective effects. Studies in rodents indicate that melatonin plays a role in the pathogenesis of hy - pertension in rats with metabolic syndrome. Piromelatine, a melatonin agonist, serotonin Introduction 5-HT-1A and 5-HT-1D agonist and serotonin 5- HT2B antagonist is a multimodal agent with sleep promoting, anti-diabetic, analgesic, anti- The pineal hormone melatonin is secreted with neurodegenerative, anxiolytic and antidepres - a marked circadian rhythm. The endogenous sant potential, currently in development for the rhythm of secretion is generated by the suprachi - treatment of insomnia. -
Product Data Sheet
Inhibitors Product Data Sheet Piromelatine • Agonists Cat. No.: HY-105285 CAS No.: 946846-83-9 Molecular Formula: C₁₇H₁₆N₂O₄ • Molecular Weight: 312.32 Screening Libraries Target: Melatonin Receptor; 5-HT Receptor; P2X Receptor; TRP Channel; Sodium Channel Pathway: GPCR/G Protein; Neuronal Signaling; Membrane Transporter/Ion Channel Storage: 4°C, protect from light * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light) SOLVENT & SOLUBILITY In Vitro DMSO : 250 mg/mL (800.46 mM; Need ultrasonic) Mass Solvent 1 mg 5 mg 10 mg Concentration Preparing 1 mM 3.2018 mL 16.0092 mL 32.0184 mL Stock Solutions 5 mM 0.6404 mL 3.2018 mL 6.4037 mL 10 mM 0.3202 mL 1.6009 mL 3.2018 mL Please refer to the solubility information to select the appropriate solvent. In Vivo 1. Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline Solubility: ≥ 2.08 mg/mL (6.66 mM); Clear solution 2. Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline) Solubility: ≥ 2.08 mg/mL (6.66 mM); Clear solution BIOLOGICAL ACTIVITY Description Piromelatine (Neu-P11) is a melatonin MT1/MT2 receptor agonist, serotonin 5-HT1A/5-HT1D agonist, and serotonin 5-HT2B antagonist. Piromelatine (Neu-P11) possesses sleep promoting, analgesic, anti-neurodegenerative, anxiolytic and antidepressant potentials. Piromelatine (Neu-P11) also possesses pain-related P2X3, TRPV1, and Nav1.7 channel-inhibition capacities[1][2][3]. IC₅₀ & Target MT1 MT2 5-HT1A Receptor 5-HT1D Receptor (Agonist) (Agonist) 5-HT2B Receptor (Antagonist) Page 1 of 3 www.MedChemExpress.com In Vivo Piromelatine (20 mg/kg, ip, daily) treatment prevents insulin resistance induced by sleep restriction[1]. -
Focus on Metabolism and Chronobiology
Focus Sci. Review Article Feb 2016, Volume 2, Issue 1 Melatonergic Treatment: Focus on Metabolism and Chronobiology Rüdiger Hardeland 1, * 1 Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, Göttingen, Germany * Corresponding author: Johann Friedrich Blumenbach Institute of Zoology and An- thropology, University of Göttingen, Berliner Str. 28, D-37073 Göttingen, Germany. Tel: +49-551395414. E-mail: [email protected] Submitted: 01.10.2016 Abstract Accepted: 02.12.2016 Introduction: Melatonin is produced in various organs, but its preferentially nocturnal synthesis and release by the pineal gland is decisive for its chronobiological actions. Keywords: The short half-life of circulating melatonin has been reason for developing synthetic Agomelatine melatonergic agonists. With regard to age- and disease-related dysfunction of the Circadian melatonergic system, treatment with melatonin or its synthetic analogs may be used for Melatonin alleviating health problems with a respective etiology. This review addresses limitations Kynuramine arising from drug-specific metabolism and disregarded chronobiological rules. Ramelteon Metabolism: Differences are illustrated by comparing the metabolism of melatonin and two approved synthetic melatonergic agonists, ramelteon and agomelatine. Apart from © 2016. Focus on Sciences hydroxylation and dealkylation reactions, melatonin can be converted to methoxylated kynuramines, a route absent in the two synthetic drugs. An unsual property is present in the ramelteon metabolite M-II, which still displays melatonergic activity, but attains 30 to 100 times higher levels than the parent compound. Two double-hydroxylated agomelatine metabolites may be involved in sometimes occurring hepatotoxicity. Chronobiology of Melatonergic Drugs: Sleep latency facilitation and readjustment of circadian rhythms require only short actions. -
Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG . -
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ASEBIO Report News and trends from the Spanish Biotech Sector and company guide 2015 Edited by Spanish Bioindustry Association (ASEBIO) All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including by photocopies, recordings or any information storage and retrieval, without written permission from the copyright holders. © ASEBIO 1st edition: september 2016 Design and editorial coordination: Cyan, Proyectos Editoriales, S.A. Index 5 The Spanish biotechnology sector in 2015 13 Companies launched in 2015 19 Business activities 29 Industrial property rights and knowledge generation 35 Health – red biotechnology 41 Agrifood – green biotechnology 45 Industrial – white biotechnology 49 Financial environment 53 Internationalisation 59 Biolatam 2015 63 Who is who? – ASEBIO Members 64 Business members 77 Other organisations 1. THE SPANISH BIOTECHNOLOGY SECTOR IN 2015 The Spanish biotechnology 1. sector in 2015 • 628 companies confirmed biotech- • Global industry turnover continued to nology to be their main and/or exclu- grow, rising to 107,788 in 2014 (13.28% sive activity (companies known as bio- more than the previous year). This growth techs), up by 13.36% compared to was in large part down to the perfor- 2013 (an increase of 74 companies mance of companies with over 250 em- compared to the previous year), mak- ployees, whose turnover grew by 17.82%. ing up for the fall of the previous year • Lastly, the contribution towards the and getting back to 2012 levels Spanish GDP of companies active in The figures reveal mixed results in the main • In net terms, 5,034 new jobs have biotechnology (another key indicator key indicators. -
A Acetylcholine Anticholinergic Drugs, 49 Cholinergic Wake-Promoting
Index A C Acetylcholine Cataplexy anticholinergic drugs, 49 GHB, 37 cholinergic wake-promoting system, 48 narcolepsy type 1, 215 cholinesterase inhibitors, 48–49 narcolepsy type 2, 215 milameline, 49 sleep-promoting orexinergic inhibitors, 46 nicotine, 49 SXB, 238–240 receptors, 48 tricyclic antidepressants, 253 sleep-promoting cholinergic Cell replacement therapy, 253 inhibitors, 49 Central sleep apnea (CSA) syndrome, 76 Adenosine Cheyne–Stokes breathing (CSB), 76 adenosine-mediated sleep-promoting Cholinesterase inhibitors system, 41 donepezil, 49 receptors, 42 physostigmine, 48 sleep-promoting adenosine receptor Chronic insomnia agonists, 42 dose discrimination, lack of, 168 wake-promoting adenosine receptor psychiatric comorbidities, 169 antagonists, 42 short-term efficacy and long-term safety, Amantadine, 77 167–168 Armodafinil sleep induction and maintenance, 168–169 chemical structure, 212 Chronic obstructive sleep apnea multiple sclerosis, 222 (OSA), 178–179 narcolepsy, 218 Chronic primary insomnia obstructive sleep apnea, 219–221 adverse effects, 165, 167 pharmacokinetics, 214 comorbid psychiatric disorders, 164 R enantiomer, 213 double-blind trial, 164 safety, 224–225 efficacy, 165 shift work disorder, 223 long-term trial, 165 open-label extension phase, 165 post hoc analysis, 165–166 B psychomotor performance, 164–165 Benzodiazepine Withdrawal Symptom rebound insomnia, 164 Questionnaire (BWSQ), 183 WASO, 164–165 © Springer International Publishing Switzerland 2015 289 A. Guglietta (ed.), Drug Treatment of Sleep Disorders, Milestones