DOCSLIB.ORG

α2-Adrenoceptor and 5-Ht3 Serotonin Receptor

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
α2-Adrenoceptor and 5-Ht3 Serotonin Receptor Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2012 α2-ADRENOCEPTOR AND 5-HT3 SEROTONIN RECEPTOR LIGANDS AS POTENTIAL ANALGESIC ADJUVANTS Genevieve Alley Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Pharmacy and Pharmaceutical Sciences Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/2867 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. © Genevieve Sirles Alley 2012 All Rights Reserved i α2-ADRENOCEPTOR AND 5-HT3 SEROTONIN RECEPTOR LIGANDS AS POTENTIAL ANALGESIC ADJUVANTS A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. by Genevieve Sirles Alley Bachelor of Science in Biology, Virginia Commonwealth University 2005 Director: Małgorzata Dukat, Ph.D. Associate Professor, Department of Medicinal Chemistry Virginia Commonwealth University Richmond, Virginia August 2012 ii ACKNOWLEDGMENT First, I would like to thank Dr. Małgorzata Dukat for her continued assistance and advice throughout my studies. This guidance has helped me better understand and appreciate medicinal chemistry. Also, a special thanks is given to both Dr. Dukat and Dr. Richard A. Glennon for their constant quizzing during group meetings, which not only helped me recongnize what I did not already understand, but also, improved my ability to devise potential solutions for future research problems. Furthermore, I could not have successfully completed this dissertation work without the help of Dr. Jin-Sung Kim as my synthetic chemistry trainer, Dr. Phil Mosier as my molecular modeling trainer and Dr. Richard Young and Shawquia Young as mentors and instructors for the behavioral animal studies. These trainers provided me with much guidance and leadership, which helped me remain optimistic and patient through the various research problems that occurred. Furthermore, I would like to thank Virginia Commonwealth University and the School of Pharmacy for giving me this opportunity as well as providing me with financial assistance for the graduate school award for dissertation writing. These studies were supported by the Jeffress Memorial Trust RG-J-778 and the A. D. Williams Trust Fund awarded to Dr. Dukat. And last but certainly not least, I would like to thank my husband, Stuart Alley, and my parents, Scott and Louisa Sirles, for their constant support and patience throughout my studies at VCU. A special thanks is given to my graduate school collegues, Jessica Worsham, Kendra Haney and Rossana Ferrera, who provided support, motivation and confidence even when I was filled with frustration and defeat. I could not have successfully completed my graduate work without all of these people in the lab and at home. ii iii TABLE OF CONTENTS List of Tables ............................................................................................................... ix List of Figures .............................................................................................................. xi List of Schemes ........................................................................................................... xxiv List of Abbreviations .................................................................................................... xxv Abstract ....................................................................................................................... xxviii I. Introduction ................................................................................................................. 1 II. Background ................................................................................................................ 7 A. Current therapy for cancer pain ........................................................................... 7 1. Nonopioid therapies ........................................................................................ 8 2. Opioid therapies ............................................................................................. 9 3. Adjuvant therapies ........................................................................................ 10 4. Pain pathways and pain control theories ...................................................... 10 B. Adrenoceptors .................................................................................................... 11 1. Classification ................................................................................................ 11 2. α2-Adrenoceptors .......................................................................................... 13 a) Structure and distribution ......................................................................... 13 b) Adrenoceptor agonists ............................................................................. 16 iii iv 1) Pharmacology and clinical relevance.................................................. 16 2) Structure-affinity relationships (SAFIRs) ............................................ 17 c) Adrenoceptor antagonists ........................................................................ 21 1) Pharmacology and clinical relevance.................................................. 21 2) Structure-affinity relationships (SAFIRs) ............................................ 21 d) Binding mode of α2-adrenoceptor agonists .............................................. 24 e) Descending control of pain ....................................................................... 25 C. Serotonin receptors ............................................................................................ 26 1. Classification ................................................................................................ 26 2. 5-HT3 receptors ............................................................................................ 29 a) Structure and distribution ......................................................................... 29 b) 5-HT3 receptor agonists ........................................................................... 31 c) 5-HT3 receptor antagonists ...................................................................... 34 d) Descending control of pain ....................................................................... 35 D. MD-354 (21) ...................................................................................................... 39 1. Binding affinity ............................................................................................... 39 2. In vitro functional activity................................................................................ 40 3. In vivo functional activity ................................................................................ 41 a) MD-354 (21) administered alone .............................................................. 41 b) MD-354 (21) administered in combination with clonidine (7) .................... 42 III. Specific aims and rationale ..................................................................................... 49 iv v A. To further investigate the mechanism of action of the analgesia-potentiating effect of clonidine (7) by MD-354 (21) ................................................................ 49 B. Exploration of conformationally-constrained rotamers of MD-354 (21) ............... 56 C. MD-354 (21) binding mode at α2-adrenoceptors ................................................ 61 IV. Results and discussion ........................................................................................... 65 A. Pharmacological studies: Nociceptive and locomotor activity animal models and binding assays ............................................................................................. 65 1. Ondansetron (23) ......................................................................................... 69 2. meta-Chlorophenylbiguanide (20; mCPBG) ................................................. 72 a) Tail-flick assay ......................................................................................... 72 b) Hot-plate assay ........................................................................................ 78 c) Locomotor activity assay .......................................................................... 81 d) Summary .................................................................................................. 83 3. SR57227A (22) ............................................................................................. 84 a) Tail-flick assay ......................................................................................... 84 b) Hot-plate assay ........................................................................................ 89 c) Locomotor activity assay .......................................................................... 91 d) Summary .................................................................................................. 93 4. TDIQ (6)........................................................................................................ 94 a) Tail-flick assay ......................................................................................... 94 b) Hot-plate assay ......................................................................................
Load more

Recommended publications
  • ALPHA ADRENOCEPTORS and HUMAN SEXUAL FUNCTION Alan
    8 1995 Elsevier Science B. V. All rights reserved. The Pharmacology of Sexual Function and Dysfunction J. Bancroft, editor 307 ALPHA ADRENOCEPTORS AND HUMAN SEXUAL FUNCTION Alan J Riley Field Place, Dunsmore, Buckinghamshire, HP22 6QH, UK Introduction Sexual functioning involves complex physiological processes which rely on the interplay of many central and peripheral neurotransmitter systems. Disturbances in any one of these systems might be associated with disturbed sexual function which, when recognised, may be alleviated by appropriate pharmacological manipulation, although at the present time this is more hypothesis than reality, The sympathetic nervous system is involved actively at various levels in the normal control of sexual responses. The effects of sympathetic activation are mediated by the release of noradrenaline from nerve terminals and the increased secretion of adrenaline from the adrenal medulla. These catecholamines selectively activate specific cellular sites in target tissues known as adrenoceptors (previously termed adrenergic receptors) to mediate responses. Almost fifty years ago, Alquist realised that tissue responses to catecholamines were mediated through two distinct types of receptors which he designated a and/? [1]. This review focuses on the involvement of a-adrenoceptors in human sexual functioning and dysfunction. Alpha adrenoceptors are located both pre- and post- synaptically and they were classified as either ar or af adrenoceptors according to location; or, being postsynaptic and az presynaptic. This classification continues to be used in some texts. However, as highly specific and selective pharmacological tools became available, this locational subclassification is found not always to be appropriate. Nowadays, classification of a-adrenoceptors is more appropriately based on pharmacological activity and additional subtypes of a-adrenoceptors have been identified by radioligand binding and molecular biological techniques [2].
    [Show full text]
  • M100907, a Serotonin 5-HT2A Receptor Antagonist and Putative Antipsychotic, Blocks Dizocilpine-Induced Prepulse Inhibition Defic
    M100907, a Serotonin 5-HT2A Receptor Antagonist and Putative Antipsychotic, Blocks Dizocilpine-Induced Prepulse Inhibition Deficits in Sprague–Dawley and Wistar Rats Geoffrey B. Varty, Ph.D., Vaishali P. Bakshi, Ph.D., and Mark A. Geyer, Ph.D. a In a recent study using Wistar rats, the serotonergic 5-HT2 1 receptor agonist cirazoline disrupts PPI. As risperidone a receptor antagonists ketanserin and risperidone reduced the and M100907 have affinity at the 1 receptor, a final study disruptive effects of the noncompetitive N-methyl-D- examined whether M100907 would block the effects of aspartate (NMDA) antagonist dizocilpine on prepulse cirazoline on PPI. Risperidone partially, but inhibition (PPI), suggesting that there is an interaction nonsignificantly, reduced the effects of dizocilpine in Wistar between serotonin and glutamate in the modulation of PPI. rats, although this effect was smaller than previously In contrast, studies using the noncompetitive NMDA reported. Consistent with previous studies, risperidone did antagonist phencyclidine (PCP) in Sprague–Dawley rats not alter the effects of dizocilpine in Sprague–Dawley rats. found no effect with 5-HT2 antagonists. To test the hypothesis Most importantly, M100907 pretreatment fully blocked the that strain differences might explain the discrepancy in effect of dizocilpine in both strains; whereas SDZ SER 082 these findings, risperidone was tested for its ability to had no effect. M100907 had no influence on PPI by itself reduce the PPI-disruptive effects of dizocilpine in Wistar and did not reduce the effects of cirazoline on PPI. These and Sprague–Dawley rats. Furthermore, to determine studies confirm the suggestion that serotonin and glutamate which serotonergic receptor subtype may mediate this effect, interact in modulating PPI and indicate that the 5-HT2A the 5-HT2A receptor antagonist M100907 (formerly MDL receptor subtype mediates this interaction.
    [Show full text]
  • )&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
    [Show full text]
  • Covalent Agonists for Studying G Protein-Coupled Receptor Activation
    Covalent agonists for studying G protein-coupled receptor activation Dietmar Weicherta, Andrew C. Kruseb, Aashish Manglikb, Christine Hillera, Cheng Zhangb, Harald Hübnera, Brian K. Kobilkab,1, and Peter Gmeinera,1 aDepartment of Chemistry and Pharmacy, Friedrich Alexander University, 91052 Erlangen, Germany; and bDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305 Contributed by Brian K. Kobilka, June 6, 2014 (sent for review April 21, 2014) Structural studies on G protein-coupled receptors (GPCRs) provide Disulfide-based cross-linking approaches (17, 18) offer important insights into the architecture and function of these the advantage that the covalent binding of disulfide-containing important drug targets. However, the crystallization of GPCRs in compounds is chemoselective for cysteine and enforced by the active states is particularly challenging, requiring the formation of affinity of the ligand-pharmacophore rather than by the elec- stable and conformationally homogeneous ligand-receptor com- trophilicity of the cross-linking function (19). We refer to the plexes. Native hormones, neurotransmitters, and synthetic ago- described ligands as covalent rather than irreversible agonists nists that bind with low affinity are ineffective at stabilizing an because cleavage may be promoted by reducing agents and the active state for crystallogenesis. To promote structural studies on disulfide transfer process is a reversible chemical reaction the pharmacologically highly relevant class
    [Show full text]
  • The Adrenergic Control of Lower Esophageal Sphincter Function: an EXPERIMENTAL MODEL of DENERVATION SUPERSENSITIVITY
    The Adrenergic Control of Lower Esophageal Sphincter Function: AN EXPERIMENTAL MODEL OF DENERVATION SUPERSENSITIVITY Anthony J. DiMarino, Sidney Cohen J Clin Invest. 1973;52(9):2264-2271. https://doi.org/10.1172/JCI107413. To evaluate the adrenergic regulation of lower esophageal sphincter (LES) function, LES pressure, LES relaxation during swallowing, and blood pressure were measured in the anesthetized opossum, Didelphis virginiana, during intravenous administration of alpha and beta adrenergic agonists and antagonists. Studies were done in controls and animals adrenergically denervated with 6-hydroxydopamine. Alpha adrenergic agonists (norepinephrine, phenylephrine) increased LES pressure and blood pressure, whereas a beta adrenergic agonist (isoproterenol) decreased both pressures. Alpha adrenergic antagonism (phentolamine) reduced basal LES pressure by 38.3±3.8% (mean ±SEM) (P < 0.001). Beta adrenergic antagonism (propranolol) had no significant effect on either basal LES pressure or percent of LES relaxation with swallowing. After adrenergic denervation with 6-hydroxydopamine, basal LES pressure was reduced by 22.5±5.3% (P < 0.025) but LES relaxation during swallowing was unaltered. In denervated animals, both LES pressure and blood pressure dose response curves showed characteristics of denervation supersensitivity to alpha but not to beta adrenergic agonists. These studies suggest: (a) a significant portion of basal LES pressure is dependent upon alpha adrenergic stimulation; (b) LES relaxation during swallowing is not an adrenergically mediated response; c( ) the LES pressure response to alpha adrenergic agonists after 6-hydroxydopamine may serve as a model of denervation supersensitivity in the gastrointestinal tract. Find the latest version: https://jci.me/107413/pdf The Adrenergic Control of Lower Esophageal Sphincter Function AN EXPERIMENTAL MODEL OF DENERVATION SUPERSENSITIVITY ANTHoNY J.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2012/0115729 A1 Qin Et Al
    US 201201.15729A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0115729 A1 Qin et al. (43) Pub. Date: May 10, 2012 (54) PROCESS FOR FORMING FILMS, FIBERS, Publication Classification AND BEADS FROM CHITNOUS BOMASS (51) Int. Cl (75) Inventors: Ying Qin, Tuscaloosa, AL (US); AOIN 25/00 (2006.01) Robin D. Rogers, Tuscaloosa, AL A6II 47/36 (2006.01) AL(US); (US) Daniel T. Daly, Tuscaloosa, tish 9.8 (2006.01)C (52) U.S. Cl. ............ 504/358:536/20: 514/777; 426/658 (73) Assignee: THE BOARD OF TRUSTEES OF THE UNIVERSITY OF 57 ABSTRACT ALABAMA, Tuscaloosa, AL (US) (57) Disclosed is a process for forming films, fibers, and beads (21) Appl. No.: 13/375,245 comprising a chitinous mass, for example, chitin, chitosan obtained from one or more biomasses. The disclosed process (22) PCT Filed: Jun. 1, 2010 can be used to prepare films, fibers, and beads comprising only polymers, i.e., chitin, obtained from a suitable biomass, (86). PCT No.: PCT/US 10/36904 or the films, fibers, and beads can comprise a mixture of polymers obtained from a suitable biomass and a naturally S3712). (4) (c)(1), Date: Jan. 26, 2012 occurring and/or synthetic polymer. Disclosed herein are the (2), (4) Date: an. AO. films, fibers, and beads obtained from the disclosed process. O O This Abstract is presented solely to aid in searching the sub Related U.S. Application Data ject matter disclosed herein and is not intended to define, (60)60) Provisional applicationpp No. 61/182,833,sy- - - s filed on Jun.
    [Show full text]
  • 5-HT3 Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: the Iceberg Still Lies Beneath the Surface
    1521-0081/71/3/383–412$35.00 https://doi.org/10.1124/pr.118.015487 PHARMACOLOGICAL REVIEWS Pharmacol Rev 71:383–412, July 2019 Copyright © 2019 by The Author(s) This is an open access article distributed under the CC BY-NC Attribution 4.0 International license. ASSOCIATE EDITOR: JEFFREY M. WITKIN 5-HT3 Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: The Iceberg Still Lies beneath the Surface Gohar Fakhfouri,1 Reza Rahimian,1 Jonas Dyhrfjeld-Johnsen, Mohammad Reza Zirak, and Jean-Martin Beaulieu Department of Psychiatry and Neuroscience, Faculty of Medicine, CERVO Brain Research Centre, Laval University, Quebec, Quebec, Canada (G.F., R.R.); Sensorion SA, Montpellier, France (J.D.-J.); Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran (M.R.Z.); and Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada (J.-M.B.) Abstract. ....................................................................................384 I. Introduction. ..............................................................................384 II. 5-HT3 Receptor Structure, Distribution, and Ligands.........................................384 A. 5-HT3 Receptor Agonists .................................................................385 B. 5-HT3 Receptor Antagonists. ............................................................385 Downloaded from 1. 5-HT3 Receptor Competitive Antagonists..............................................385 2. 5-HT3 Receptor
    [Show full text]
  • Stems for Nonproprietary Drug Names
    USAN STEM LIST STEM DEFINITION EXAMPLES -abine (see -arabine, -citabine) -ac anti-inflammatory agents (acetic acid derivatives) bromfenac dexpemedolac -acetam (see -racetam) -adol or analgesics (mixed opiate receptor agonists/ tazadolene -adol- antagonists) spiradolene levonantradol -adox antibacterials (quinoline dioxide derivatives) carbadox -afenone antiarrhythmics (propafenone derivatives) alprafenone diprafenonex -afil PDE5 inhibitors tadalafil -aj- antiarrhythmics (ajmaline derivatives) lorajmine -aldrate antacid aluminum salts magaldrate -algron alpha1 - and alpha2 - adrenoreceptor agonists dabuzalgron -alol combined alpha and beta blockers labetalol medroxalol -amidis antimyloidotics tafamidis -amivir (see -vir) -ampa ionotropic non-NMDA glutamate receptors (AMPA and/or KA receptors) subgroup: -ampanel antagonists becampanel -ampator modulators forampator -anib angiogenesis inhibitors pegaptanib cediranib 1 subgroup: -siranib siRNA bevasiranib -andr- androgens nandrolone -anserin serotonin 5-HT2 receptor antagonists altanserin tropanserin adatanserin -antel anthelmintics (undefined group) carbantel subgroup: -quantel 2-deoxoparaherquamide A derivatives derquantel -antrone antineoplastics; anthraquinone derivatives pixantrone -apsel P-selectin antagonists torapsel -arabine antineoplastics (arabinofuranosyl derivatives) fazarabine fludarabine aril-, -aril, -aril- antiviral (arildone derivatives) pleconaril arildone fosarilate -arit antirheumatics (lobenzarit type) lobenzarit clobuzarit -arol anticoagulants (dicumarol type) dicumarol
    [Show full text]
  • Antihypertensive Agents Using ALZET Osmotic Pumps
    ALZET® Bibliography References on the Administration of Antihypertensive Agents Using ALZET Osmotic Pumps 1. Atenolol Q7652: W. B. Zhao, et al. Stimulation of beta-adrenoceptors up-regulates cardiac expression of galectin-3 and BIM through the Hippo signalling pathway. British Journal of Pharmacology 2019;176(14):2465-2481 Agents: Isoproterenol; propranolol; carvedilol; atenolol; ICI-118551 Vehicle: saline; ascorbic acid, buffered; Route: SC; Species: Mice; Pump: 2001; Duration: 1 day; 2 days; 7 days; ALZET Comments: Dose ((ISO 0.6, 6, 20 mg/kg/d), (Prop 2 mg/kg/d), (Carv 2 mg/kg/d), (AT 2 mg/kg/d), (ICI 1 mg/kg/d)); saline with 0.4 mM ascorbic acid used; Controls were non-transgenic and received mp w/ vehicle; animal info (12-16 weeks, Male, (C57BL/6J, beta2-TG, Mst1-TG, or dnMst1-TG)); ICI-118551 is a beta2-antagonist with the structure (2R,3S)-1-[(7-methyl-2,3-dihydro-1H-inden-4-yl)oxy]-3-(propan-2-ylamino)butan-2-ol; cardiovascular; Minipumps were removed to allow for washout of ISO overnight prior to imaging; Q7241: M. N. Nguyen, et al. Mechanisms responsible for increased circulating levels of galectin-3 in cardiomyopathy and heart failure. Sci Rep 2018;8(1):8213 Agents: Isoproterenol, Atenolol, ICI-118551 Vehicle: Saline, ascorbic acid; Route: SC; Species: Mice; Pump: Not Stated; Duration: 48 Hours; ALZET Comments: Dose: ISO (2, 6 or 30 mg/kg/day; atenolol (2 mg/kg/day), ICI-118551 (1 mg/kg/day); 0.4 mM ascorbic used; animal info (12 14 week-old C57Bl/6 mice); cardiovascular; Q6161: C.
    [Show full text]
  • Pharmacological Approach to Sleep Disturbances in Autism Spectrum Disorders with Psychiatric Comorbidities: a Literature Review
    medical sciences Review Pharmacological Approach to Sleep Disturbances in Autism Spectrum Disorders with Psychiatric Comorbidities: A Literature Review Sachin Relia 1,* and Vijayabharathi Ekambaram 2,* 1 Department of Psychiatry, University of Tennessee Health Sciences Center, 920, Madison Avenue, Suite 200, Memphis, TN 38105, USA 2 Department of Psychiatry, University of Oklahoma Health Sciences Center, 920, Stanton L Young Blvd, Oklahoma City, OK 73104, USA * Correspondence: [email protected] (S.R.); [email protected] (V.E.); Tel.: +1-901-448-4266 (S.R.); +1-405-271-5251 (V.E.); Fax: +1-901-297-6337 (S.R.); +1-405-271-3808 (V.E.) Received: 15 August 2018; Accepted: 17 October 2018; Published: 25 October 2018 Abstract: Autism is a developmental disability that can cause significant emotional, social and behavioral dysfunction. Sleep disorders co-occur in approximately half of the patients with autism spectrum disorder (ASD). Sleep problems in individuals with ASD have also been associated with poor social interaction, increased stereotypy, problems in communication, and overall autistic behavior. Behavioral interventions are considered a primary modality of treatment. There is limited evidence for psychopharmacological treatments in autism; however, these are frequently prescribed. Melatonin, antipsychotics, antidepressants, and α agonists have generally been used with melatonin, having a relatively large body of evidence. Further research and information are needed to guide and individualize treatment for this population group. Keywords: autism spectrum disorder; sleep disorders in ASD; medications for sleep disorders in ASD; comorbidities in ASD 1. Introduction Autism is a developmental disability that can cause significant emotional, social, and behavioral dysfunction. According to the Diagnostic and Statistical Manual (DSM-V) classification [1], autism spectrum disorder (ASD) is characterized by persistent deficits in domains of social communication, social interaction, restricted and repetitive patterns of behavior, interests, or activities.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2005/0049256A1 Lorton Et Al
    US 2005.0049256A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0049256A1 LOrton et al. (43) Pub. Date: Mar. 3, 2005 (54) TREATMENT OF INFLAMMATORY Publication Classification AUTOIMMUNE DISEASES WITH ALPHA-ADRENERGIC ANTAGONSTS AND BETA-ADRENERGICAGONSTS (51) Int. Cl." ...................... A61K 31/517; A61K 31/137 (76) Inventors: Dianne Lorton, Avondale, AZ (US); (52) U.S. Cl. ..................... 514/252.17; 514/649; 514/651 Cheri Lubahn, Glendale, AZ (US) Correspondence Address: JENNINGS, STROUSS & SALMON, P.L.C. (57) ABSTRACT 201 E. WASHINGTON ST, 11TH FLOOR PHOENIX, AZ 85004 (US) The present invention discloses a novel compound and (21) Appl. No.: 10/928,437 method for the treatment of inflammatory autoimmune dis eases, for example, rheumatoid arthritis, using C.-adrenergic (22) Filed: Aug. 27, 2004 antagonists and B-adrenergic agonists in combination. Treat ment of animals, namely humans, with an O-adrenergic Related U.S. Application Data antagonist, preferably, phentolamine, and a B-adrenergic agonist, preferably terbutaline, in combination can Signifi (60) Provisional application No. 60/498.367, filed on Aug. cantly Suppress the joint destruction and inflammation due to 27, 2003. disease in these animals. Patent Application Publication Mar. 3, 2005 Sheet 1 of 5 US 2005/0049256A1 Patent Application Publication Mar. 3, 2005 Sheet 2 of 5 US 2005/0049256A1 e \ s o o (ulu) pA ped)00 IBuedos. IOC Patent Application Publication Mar. 3, 2005 Sheet 3 of 5 US 2005/0049256A1 as o N w N o et N O CY) c5 O t al L cN Y D. a s t is r s re y (uu) supW pedoo Patent Application Publication US 2005/004925.6 A1 |0*>d 0|| eIOOS 3 guide foupe Patent Application Publication Mar.
    [Show full text]
  • The Use of Stems in the Selection of International Nonproprietary Names (INN) for Pharmaceutical Substances
    WHO/PSM/QSM/2006.3 The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances 2006 Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Medicines Policy and Standards The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 © World Health Organization 2006 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
    [Show full text]