'T ' Indicate Tables. 3PPP, 380F 5HIAA (5-Hydro

Total Page:16

File Type:pdf, Size:1020Kb

'T ' Indicate Tables. 3PPP, 380F 5HIAA (5-Hydro Cambridge University Press 978-0-521-8570 2-4 - Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, Third Edition Stephen M. Stahl Index More information Index Page numbers followed by ‘f ’ indicate figures; page numbers followed by ‘t ’ indicate tables. 3PPP, 380f acetylcholine neurotransmitter, 128t 5HIAA (5-hydroxy-indole acetic acid), 483 as psychotropic drug target, 115, 117 in cerebrospinal fluid, 488 acetylcholine receptors, TCA and, 602f acetylcholine transporters, 94t,99f AAADC (aromatic amino acid decarboxylase), acetylcholinesterase (AChE), 112, 170, 915, 343, 344f 915f AAB-001, 937 donepezil to inhibit, 925f “able stabilizers”, 717, 717f galantamine to inhibit, 930f ABT089, 449 rivastigmine to inhibit, 928f abuse, 945 ACh. See acetylcholine (ACh) acamprosate, 769 ACP 103, 446 actions, in ventral tegmental area (VTA), ACP-104, 375, 380f 978f ACR16, 380f for alcohol dependency, 976 ACTH (adrenocorticotropic hormone), 752, in combos for bipolar disorder, 715 753f icon, 976f actin, 36, 42f ACC-001, 937 action potential, 145, 159, 160f acetyl coenzyme A (AcCoA), as acetylcholine control over firing, 217 precursor, 914 encoding of, 162f acetylcholine (ACh), 139, 902 ionic components of, 147f in arousal pathways, 396, 398f activity-dependent nociception, 795 and arousal spectrum, 817, 817f acute pain, 796f and blocked dopamine receptors, 339f neuropathic pain, 797f overactivity, 341 activity-dependent spine formation, by production, 914, 914f estradiol, 614f projections, 206, 207f acute pain, 774, 775, 796f via basal forebrain, 208f vs. chronic, 775t psychotropic drugs and, 53, 99, 128, 129 acute stress reaction, 193 reciprocal relationship with dopamine, 338f Adapin. See doxepin (Sinequan, Adapin) and reward, 946, 947f adaptive states, 138 termination of action, 915f adatanserin, 574 for treating nicotine dependence, 960 addiction, 945, 953f. See also substance abuse vesicular transporter for, 102 nicotine and, 955–959 acetylcholine-linked mechanisms, 448 overvalued reward in, 951 1057 © Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-8570 2-4 - Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, Third Edition Stephen M. Stahl Index More information adenosine, 820, 859 agonists adenylate cyclase, binding to G protein, 70 absence of, 108, 112f ADHD. See attention deficit hyperactivity actions on ion channel, 133f disorder (ADHD) antagonist acting in presence of, 135f adhesion molecules, 31 and G protein-linked receptor, 110–112 and neuronal migration, 30f impact on ligand-gated ion channels, adipose tissue, insulin resistance in, 387, 390f 143f adolescence spectrum, 111f aggressiveness in, 425 and receptor conformation, 378f antidepressants for, 519f agoraphobia, in children, 713 brain restructuring in, 22, 22f,44 agranulocytosis, clozapine and, 410 mania in, 712 akathisia removal of synaptic connections, 42, 314 from aripiprazole, 421 risperidone for treating psychotic disorders, nigrostrial pathway dopamine deficiencies 412 and, 277 adrenocorticotropic hormone (ACTH), 752, from paroxetine withdrawal, 537 753f from SSRIs, 531 affective blunting, 251 alanine-serine-cysteine transporter (ASC-T), affective disorders, 454. See also mood disorders glial, 280 stress-induced, novel treatments, 754f alcohol, affective flattening, as SSRI side effect, 356 actions affective spectrum disorders, 556, 776t on reward circuits, 971f norepinephrine and, 546 in ventral tegmental area (VTA), 972f pain in, 802 consumption, vs. sleepiness, 851t “affective storms”, in children, 712 dependency/abuse affective symptoms by ADHD patients, 870 dorsal vs. ventral regulation, 322f social anxiety and, 769 mesolimbic dopamine pathway role in, 274 treatment, 973–977 multiple disorders impacting, 261f GABA-A receptor binding to, 737 pharmacy, 428, 430f heavy drinking in schizophrenia, shared with other disorders, vs. reduced-risk, 973 260 will power to reduce, 975f afferent neurons, peripheral, neuropathic pain icon, 970f and, 785 probability of dependence, 968t age. See also adolescence; children; elderly reduced-risk drinking, 975t synapse formation by, 49f and reward, 970 aggressive symptom pharmacy, 425, 427f alcoholics, smoking by, 970 aggressiveness, 256, 704f aldehyde dehydrogenase, 977 in dementia patients, 935 alertness, 650 multiple disorders impacting, 261f loss in schizophrenic patients, 259 bupropion for, 556 Agilect/Azilect (rasaligine), 579t as SSRI side effect, 530 for Parkinson’s disease, 582 allodynia, 775, 786, 795, 799f aging. See also elderly allosteric modulation, 140, 737, 738 erectile dysfunction and, 1000f alogia, 251, 252t hippocampus sensitivity to, 24, 24f alpha 1 adrenergic receptors normal, 908 atypical antipsychotic agents and, 385f and synapse loss, 25f and sedation, 397f agitation, 547 TCA and, 599, 603f benzodiazepines for, 434 alpha 1 antagonist, for posttraumatic stress in dementia patients, 935 disorder, 770 agnosia, 900 alpha-1 receptor, antagonism, 340f agomelatine (Valdoxan), 574, 658, 844f alpha 1 selective hypnotics, 840f icon, 661f alpha-1 unit, 153, 154f 1058 Index © Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-8570 2-4 - Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, Third Edition Stephen M. Stahl Index More information alpha-2 adrenergic receptors, atypical Aβ42 oligomer interference with synaptic antipsychotic agents and, 385f function, 906, 906f alpha 2 antagonists, 414 Aβ42 production, 905f icon, 559f inflammation from plaque formation, and norepinephrine, 560f 907f and serotonin, 560f neuronal dysfunction and loss, 909f as serotonin norepinephrine disinhibitors, tangle formation, 908f 558, 562f amyloid plaques in, 901 alpha 2 delta ligands, 156, 158f Apo-E protein and, 907, 910f for anxiety disorders, 755 cholinergic deficiency, 920 binding of, 798f cholinesterase inhibitors for chronic pain, 801f best responders, 922, 922f in dorsal horn, 800f donepezil, 923, 924f for fibromyalgia, 808 galantamine, 926 and pain gate, 795 palliative responders, 924f potential therapeutic effects, 756f rivastigmine, 924, 926f alpha-2 delta protein, 153 tacrine, 923 gabapentin and pregabalin binding to, treatment outcomes, 921 158 usual responders, 923f alpha-2 delta unit, 155f clinical features, 901t alpha 2 receptors cognitive symptoms, 259 on axon terminal, 478f excitotoxicity and, 48f, 302, 303f blockade of, 559f expected exponential increase, 901 somatodendritic, 475, 479f familial cases early onset, 906 alpha 2A agonists, 891 folate for depression, 935 mechanism of action, 895f glutamate hypothesis of cognitive deficiency, alpha-4 beta-2 nicotinic acetylcholine receptor, 926–930 449 identifying at presymptomatic/prodromal alpha 4 beta 2 nicotinic receptors, 959, 960f stage, 911f reinforcement and, 958f neurofibrillary tangles in, 901 alpha-7-nicotinic cholinergic agonists, 448 problems with studies of, 912 alpha 7 nicotinic cholinergic receptors, 918 symptom pattern onset, 913f alpha amino-3-hydroxy-5-methyl-4- symptomatic treatments in development, 940 isoxazolepropionic acid (AMPA) symptoms shared with schizophrenia, 258, receptors, 286, 286f 259, 259f synapses with, 313f treatment, 128, 129 alpha APP, 903 untreated time course, 921f alpha heliz, 109f amantadine, 440 alpha-L-glutamyl transferace, 627 for bipolar disorder, 695 alpha pore icon, 696f of voltage-sensitive calcium channels, 154f mechanism of action of voltage-sensitive sodium channels, 151f on GABA, glutamate, sigma, and anticonvulsant binding, 151 dopamine, 676t alpha secretase, 902 VSSCs, synaptic vesicles, and carbonic alpha subunit, 147, 148f anhydrase, 675t alprazolam (Xanax), 53 possible actions in bipolar disorder, 698f and CYP 450 3A4, 608 putative clinical actions, 673t and sedation, 609 amenorrhea, 278, 336 alprostadil, 1004 American College of Rheumatology, criteria for ALS (amyotrophic lateral sclerosis) fibromyalgia, 805t excitotoxicity and, 48f American Psychiatric Association, 178 riluzole for, 685f amibegron, 662 Alzheimer’s disease, 426, 900 amines, 52t amyloid cascade hypothesis, 902 d-amino acid oxidase (DAO), 284f Index 1059 © Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-8570 2-4 - Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, Third Edition Stephen M. Stahl Index More information amino acid transporters, 94t manic episode symptoms linked to, 506 inhibitory, 94t noradrenergic receptor simulation in, 547 amino acids, 52t overactive circuits, 745f to close VSSC, 148 regulating anxiety in, 241 for ligand-gated ion channels, 126 response to emotional input, 324 regulation of calcium channels, 153 and schizophrenia symptoms, 262f in voltage-gated ion channels, 147 serotonin and fear processing by, 234 amisulpride, 376, 380f amylin, 450 and cardiometabolic risk, 386t amyloid, and glutamate steady leak, 928 clinical actions of, 371 amyloid cascade hypothesis for Alzheimer’s and diabetes, 417 disease, 902, 905f for negative symptoms in schizophrenia, neuronal dysfunction and loss, 909f 428f amyloid plaques, 903 pharmacological icon, 423f in Alzheimer’s disease, 901 and QTc prolongation, 417 and glutamate excitotoxicity, 932f amitriptyline (Elavil, Endep, Tryptizol, and glutamate release, 927 Loroxyl), 53, 572, 597t treatment development to act on, 937 amnesia, 900 amyloid precursor protein (APP), 902 amotivational syndrome, 986 processing into Aβ peptides, amoxapine (Asendin), 419, 420f
Recommended publications
  • (19) United States (12) Patent Application Publication (10) Pub
    US 20130289061A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0289061 A1 Bhide et al. (43) Pub. Date: Oct. 31, 2013 (54) METHODS AND COMPOSITIONS TO Publication Classi?cation PREVENT ADDICTION (51) Int. Cl. (71) Applicant: The General Hospital Corporation, A61K 31/485 (2006-01) Boston’ MA (Us) A61K 31/4458 (2006.01) (52) U.S. Cl. (72) Inventors: Pradeep G. Bhide; Peabody, MA (US); CPC """"" " A61K31/485 (201301); ‘4161223011? Jmm‘“ Zhu’ Ansm’ MA. (Us); USPC ......... .. 514/282; 514/317; 514/654; 514/618; Thomas J. Spencer; Carhsle; MA (US); 514/279 Joseph Biederman; Brookline; MA (Us) (57) ABSTRACT Disclosed herein is a method of reducing or preventing the development of aversion to a CNS stimulant in a subject (21) App1_ NO_; 13/924,815 comprising; administering a therapeutic amount of the neu rological stimulant and administering an antagonist of the kappa opioid receptor; to thereby reduce or prevent the devel - . opment of aversion to the CNS stimulant in the subject. Also (22) Flled' Jun‘ 24’ 2013 disclosed is a method of reducing or preventing the develop ment of addiction to a CNS stimulant in a subj ect; comprising; _ _ administering the CNS stimulant and administering a mu Related U‘s‘ Apphcatlon Data opioid receptor antagonist to thereby reduce or prevent the (63) Continuation of application NO 13/389,959, ?led on development of addiction to the CNS stimulant in the subject. Apt 27’ 2012’ ?led as application NO_ PCT/US2010/ Also disclosed are pharmaceutical compositions comprising 045486 on Aug' 13 2010' a central nervous system stimulant and an opioid receptor ’ antagonist.
    [Show full text]
  • Modifications to the Harmonized Tariff Schedule of the United States To
    U.S. International Trade Commission COMMISSIONERS Shara L. Aranoff, Chairman Daniel R. Pearson, Vice Chairman Deanna Tanner Okun Charlotte R. Lane Irving A. Williamson Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement the Dominican Republic- Central America-United States Free Trade Agreement With Respect to Costa Rica Publication 4038 December 2008 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 18, 2008, set forth in the Appendix hereto, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement the Dominican Republic- Central America-United States Free Trade Agreement, as approved in the Dominican Republic-Central America- United States Free Trade Agreement Implementation Act, with respect to Costa Rica. (This page is intentionally blank) Annex I Effective with respect to goods that are entered, or withdrawn from warehouse for consumption, on or after January 1, 2009, the Harmonized Tariff Schedule of the United States (HTS) is modified as provided herein, with bracketed matter included to assist in the understanding of proclaimed modifications. The following supersedes matter now in the HTS. (1). General note 4 is modified as follows: (a). by deleting from subdivision (a) the following country from the enumeration of independent beneficiary developing countries: Costa Rica (b).
    [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]
  • Pharmaceutical Appendix to the Tariff Schedule 2
    Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 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. ABACAVIR 136470-78-5 ACIDUM LIDADRONICUM 63132-38-7 ABAFUNGIN 129639-79-8 ACIDUM SALCAPROZICUM 183990-46-7 ABAMECTIN 65195-55-3 ACIDUM SALCLOBUZICUM 387825-03-8 ABANOQUIL 90402-40-7 ACIFRAN 72420-38-3 ABAPERIDONUM 183849-43-6 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABATACEPTUM 332348-12-6 ACITEMATE 101197-99-3 ABCIXIMAB 143653-53-6 ACITRETIN 55079-83-9 ABECARNIL 111841-85-1 ACIVICIN 42228-92-2 ABETIMUSUM 167362-48-3 ACLANTATE 39633-62-0 ABIRATERONE 154229-19-3 ACLARUBICIN 57576-44-0 ABITESARTAN 137882-98-5 ACLATONIUM NAPADISILATE 55077-30-0 ABLUKAST 96566-25-5 ACODAZOLE 79152-85-5 ABRINEURINUM 178535-93-8 ACOLBIFENUM 182167-02-8 ABUNIDAZOLE 91017-58-2 ACONIAZIDE 13410-86-1 ACADESINE 2627-69-2 ACOTIAMIDUM 185106-16-5 ACAMPROSATE 77337-76-9
    [Show full text]
  • Rationale, Pharmacology and Clinical Efficacy of Partial Agonists of A4b2
    Opinion TRENDS in Pharmacological Sciences Vol.28 No.7 Rationale, pharmacology and clinical efficacy of partial agonists of a4b2 nACh receptors for smoking cessation Hans Rollema1, Jotham W. Coe2, Leslie K. Chambers1, Raymond S. Hurst1, Stephen M. Stahl4 and Kathryn E. Williams3 1 Department of Neuroscience Biology, Pfizer Global Research and Development, Groton, CT 06340, USA 2 Department of Chemistry, Pfizer Global Research and Development, Groton, CT 06340, USA 3 Department of Clinical Development, Pfizer Global Research and Development, Groton, CT 06340, USA 4 Department of Psychiatry, University of California at San Diego, 1930 Palomar Point Way, Suite 103 Carlsbad, CA 92008, USA Most smokers repeatedly fail in their attempts to stop [7–9]. Cigarettes are particularly addictive because they smoking because of the addictive nature of the nicotine are readily available and are extremely efficient at deliver- in tobacco products. Nicotine dependence is probably ing the neuroactive components of tobacco to the brain. In mediated through the activation of multiple subtypes essence, cigarettes provide, with each inhalation, indivi- of neuronal nicotinic acetylcholine receptor (nAChR), dualized control over the amount and frequency of nicotine among which the mesolimbic a4b2 subtype has a pivotal that is delivered to the brain and, thus, over mesolimbic role. Here, we discuss the rationale for and the design of dopamine (DA) neurotransmission – a crucial element of a4b2 nAChR partial agonists as novel treatments for the response to addictive substances. The rapid and tran- tobacco addiction. Such agents are expected to exhibit sient increases in DA release in the nucleus accumbens a dual action by sufficiently stimulating a4b2-nAChR- that inhaled nicotine produces will initiate and sustain mediated dopamine release to reduce craving when compulsive substance-seeking behavior and drug depen- quitting and by inhibiting nicotine reinforcement when dence in humans, as described for other drugs of abuse.
    [Show full text]
  • Latest Reviews from Cochrane
    EVIDENCE-BASED MEDICINE n Latest reviews from Cochrane In this section we present an abstract of a review relevant to prescribing in general practice from the latest issue of The Cochrane Database of Systematic Reviews. To view the article in full or for further information, visit www.thecochranelibrary.com Main results detected no significant excess of The authors identified 12 treatment-spe - neuropsychiatric events (RR 0.53; cific reviews. The analyses covered 267 0.17 –1.67) or of cardiac events (RR 1.26; studies, involving 101 804 participants. 0.62 –2.56). Pharmacological interventions Both NRT and bupropion were superior to Nortriptyline increased the chances for smoking cessation: an placebo (odds ratio – OR 1.84; 95% CI of quitting (RR 2.03; 1.48 –2.78). Neither overview and network meta- 1.71 –1.99, and 1.82; 1.60 –2.06 respec - nortriptyline nor bupropion were shown analysis tively). Varenicline also increased the to enhance the effect of NRT compared odds of quitting compared with placebo with NRT alone. Clonidine increased the Objectives (OR 2.88; 2.40 –3.47). chances of quitting (RR 1.63; 1.22 –2.18), Smoking is the leading preventable cause Head-to-head comparisons between but this was offset by a dose-dependent of illness and premature death worldwide. bupropion and NRT showed equal effi - rise in adverse events. Other treatments Some medications have been proven to cacy (OR 0.99; 0.86 –1.13). Varenicline failed to demonstrate a benefit compared help people to quit, with three licensed for was superior to single forms of NRT (OR with placebo.
    [Show full text]
  • Involvement of Nicotinic Receptor Subtypes in the Behavioral Effects of Nicotinic Drugs in Squirrel Monkeys
    1521-0103/366/2/397–409$35.00 https://doi.org/10.1124/jpet.118.248070 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 366:397–409, August 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Involvement of Nicotinic Receptor Subtypes in the Behavioral Effects of Nicotinic Drugs in Squirrel Monkeys Sarah L. Withey,1 Michelle R. Doyle,1,2 Jack Bergman, and Rajeev I. Desai Preclinical Pharmacology Laboratory, McLean Hospital/Harvard Medical School, Belmont, Massachusetts Received January 27, 2018; accepted May 17, 2018 ABSTRACT Evidence suggests that the a4b2, but not the a7, subtype of the except for lobeline, the nicotinic agonists produced either full nicotinic acetylcholine receptor (nAChR) plays a key role in [(1)-epibatidine, (2)-epibatidine, and nicotine] or partial (vare- Downloaded from mediating the behavioral effects of nicotine and related drugs. nicline, cytisine, anabaseine, and isoarecolone) substitution for However, the importance of other nAChR subtypes remains (1)-epibatidine. In interaction studies with antagonists differing unclear. The present studies were conducted to examine the in selectivity, (1)-epibatidine discrimination was substan- involvement of nAChR subtypes by determining the effects of tively antagonized by mecamylamine, slightly attenuated selected nicotinic agonists and antagonists in squirrel monkeys by hexamethonium (peripherally restricted) or dihydro- b a either 1) responding for food reinforcement or 2) discriminating the -erythroidine, and not altered by methyllycaconitine ( 7 jpet.aspetjournals.org nicotinic agonist (1)-epibatidine (0.001 mg/kg) from vehicle. In selective). Varenicline and cytisine enhanced (1)-epibati- food-reinforcement studies, nicotine, (1)-epibatidine, varenicline dine’s discriminative-stimulus effects.
    [Show full text]
  • I Regulations
    23.2.2007 EN Official Journal of the European Union L 56/1 I (Acts adopted under the EC Treaty/Euratom Treaty whose publication is obligatory) REGULATIONS COUNCIL REGULATION (EC) No 129/2007 of 12 February 2007 providing for duty-free treatment for specified pharmaceutical active ingredients bearing an ‘international non-proprietary name’ (INN) from the World Health Organisation and specified products used for the manufacture of finished pharmaceuticals and amending Annex I to Regulation (EEC) No 2658/87 THE COUNCIL OF THE EUROPEAN UNION, (4) In the course of three such reviews it was concluded that a certain number of additional INNs and intermediates used for production and manufacture of finished pharmaceu- ticals should be granted duty-free treatment, that certain of Having regard to the Treaty establishing the European Commu- these intermediates should be transferred to the list of INNs, nity, and in particular Article 133 thereof, and that the list of specified prefixes and suffixes for salts, esters or hydrates of INNs should be expanded. Having regard to the proposal from the Commission, (5) Council Regulation (EEC) No 2658/87 of 23 July 1987 on the tariff and statistical nomenclature and on the Common Customs Tariff (1) established the Combined Nomenclature Whereas: (CN) and set out the conventional duty rates of the Common Customs Tariff. (1) In the course of the Uruguay Round negotiations, the Community and a number of countries agreed that duty- (6) Regulation (EEC) No 2658/87 should therefore be amended free treatment should be granted to pharmaceutical accordingly, products falling within the Harmonised System (HS) Chapter 30 and HS headings 2936, 2937, 2939 and 2941 as well as to designated pharmaceutical active HAS ADOPTED THIS REGULATION: ingredients bearing an ‘international non-proprietary name’ (INN) from the World Health Organisation, specified salts, esters or hydrates of such INNs, and designated inter- Article 1 mediates used for the production and manufacture of finished products.
    [Show full text]
  • Orthosteric and Allosteric Ligands of Nicotinic Acetylcholine Receptors for Smoking Cessation
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Frontiers - Publisher Connector MINI REVIEW published: 25 November 2015 doi: 10.3389/fnmol.2015.00071 Orthosteric and Allosteric Ligands of Nicotinic Acetylcholine Receptors for Smoking Cessation Tasnim S. Mohamed 1, Selwyn S. Jayakar 2 and Ayman K. Hamouda 1,3* 1 Department of Pharmaceutical Sciences, College of Pharmacy, Texas A&M Health Sciences Center, Kingsville, TX, USA, 2 Department of Neurobiology, Harvard Medical School, Boston, MA, USA, 3 Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M Health Sciences Center, Bryan, TX, USA Nicotine addiction, the result of tobacco use, leads to over six million premature deaths world-wide per year, a number that is expected to increase by a third within the next two decades. While more than half of smokers want and attempt to quit, only a small percentage of smokers are able to quit without pharmacological interventions. Therefore, over the past decades, researchers in academia and the pharmaceutical industry have focused their attention on the development of more effective smoking cessation therapies, which is now a growing 1.9 billion dollar market. Because the role of neuronal nicotinic acetylcholine receptors (nAChR) in nicotine addiction is well established, nAChR based therapeutics remain the leading strategy for smoking cessation. However, the development of neuronal nAChR drugs that are selective for a nAChR subpopulation is challenging, and only few neuronal nAChR drugs are clinically available. Among the many neuronal nAChR subtypes that have been identified in the brain, the a4b2 subtype is the most abundant and plays a critical role in nicotine addiction.
    [Show full text]
  • Effects of Varenicline on Sympatho
    Haarmann et al. Tobacco Induced Diseases (2016) 14:26 DOI 10.1186/s12971-016-0091-x RESEARCH Open Access Effects of varenicline on sympatho-vagal balance and cue reactivity during smoking withdrawal: a randomised placebo-controlled trial Helge Haarmann1†, Alexandra Gossler1†, Peter Herrmann2, Slavtcho Bonev3, Xuan Phuc Nguyen3, Gerd Hasenfuß1, Stefan Andreas1,4 and Tobias Raupach1,5* Abstract Background: Varenicline is an effective smoking cessation medication. Some concern has been raised that its use may precipitate adverse cardiovascular events although no patho-physiological mechanism potentially underlying such an effect has been reported. The aim of this study was to test the hypothesis that varenicline impacts on sympatho-vagal balance during smoking withdrawal. Methods: In this randomised, placebo-controlled trial, muscle sympathetic nerve activity (MSNA), baroreflex sensitivity (BRS), heart rate, and blood pressure were assessed in 17 smokers four weeks before a quit attempt (baseline) and again on the third day of that quit attempt (acute smoking withdrawal). Results: Regarding the primary endpoint of our study, we did not find a significant effect of varenicline compared to placebo on changes in MSNA burst incidence between baseline and acute smoking withdrawal (−3.0 ± 3.3 vs.−3.9 ± 5.0 bursts/100 heart beats; p = 0.308). However, heart rate and systolic blood pressure significantly decreased in the placebo group only, while no significant changes in these parameters were observed in the varenicline group. Exposure to smoking cues during acute withdrawal lead to a significant increase of heart rate in the placebo group, while heart rate decreased in the varenicline group, and the difference in these changes was significant between groups (+2.7 ± 1.0 vs.−1.8 ± 0.5 1/min; p = 0.002).
    [Show full text]
  • Molecular Actions of Smoking Cessation Drugs at Α4β2 Nicotinic Receptors Defined in Crystal Structures of a Homologous Binding Protein
    Molecular actions of smoking cessation drugs at α4β2 nicotinic receptors defined in crystal structures of a homologous binding protein Bert Billena, Radovan Spurnya, Marijke Bramsa, René van Elkb, Soledad Valera-Kummerc, Jerrel L. Yakeld, Thomas Voetse, Daniel Bertrandc, August B. Smitb, and Chris Ulensa,1 aLaboratory of Structural Neurobiology, KU Leuven, 3000 Leuven, Belgium; bDepartment of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV, Amsterdam, The Netherlands; cHiQScreen, 1211 Geneva, Switzerland; dLaboratory of Neurobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 22709; and eLaboratory of Ion Channel Research, KU Leuven, 3000 Leuven, Belgium Edited by Palmer Taylor, University of California at San Diego, La Jolla, CA, and accepted by the Editorial Board April 26, 2012 (received for review October 5, 2011) Partial agonists of the α4β2 nicotinic acetylcholine receptor domain in complex with α-bungarotoxin (16). However, signifi- (nAChR), such as varenicline, are therapeutically used in smoking cant progress has been made since the discovery of water-soluble cessation treatment. These drugs derive their therapeutic effect pentameric acetylcholine binding proteins (AChBPs) from snails from fundamental molecular actions, which are to desensitize and the subsequent elucidation of their high-resolution ligand- α4β2 nAChRs and induce channel opening with higher affinity, bound crystal structures. AChBPs are homologs of the extracel- but lower efficacy than a full agonist at equal receptor occupancy. lular domain of nAChRs and are the best-studied structural Here, we report X-ray crystal structures of a unique acetylcholine models of ligand recognition by the extracellular domain of binding protein (AChBP) from the annelid Capitella teleta, Ct- nAChRs (17–19).
    [Show full text]
  • New Horizons for Therapeutics in Drug and Alcohol Abuse
    Pharmacology & Therapeutics 125 (2010) 138–168 Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Associate editor: G. Dusting New horizons for therapeutics in drug and alcohol abuse Bianca Jupp a, Andrew J. Lawrence a,b,⁎ a Florey Neuroscience Institutes, The University of Melbourne, Parkville VIC 3010, Australia b The Centre for Neuroscience, The University of Melbourne, Parkville VIC 3010, Australia article info abstract Keywords: Alcohol, tobacco and illicit drug dependence represents a serious health and social issue within the Addiction community. As drug dependence has become more widely recognized as a clinical disorder and the severity Amphetamine of the problem been fully realized, options available for treatment have grown along with our understanding Cannabis of the neurobiological mechanisms underlying the development and persistence of addiction. Treatment has Cocaine progressed from purely social and behavioral approaches to now encompass pharmacotherapy to attempt to Inhalants Nicotine disrupt the mechanisms underlying these disorders. Despite these advances, many forms of addiction lack effective therapeutics and the prevalence of this disorder remains unacceptably high. As a result, a significant effort within the research community has been dedicated to the identification of novel targets for the development of therapeutics based upon our understanding of the pathological processes underlying addiction. The current review aims to provide an overview of existing and clinically trialed pharmacothera- pies for alcohol, opiate, psychostimulant, nicotine, cannabis and inhalant addictions. Further, we discuss some of the potential targets that have been recently indentified from basic studies that may hold promise for the development of novel treatments. © 2009 Elsevier Inc.
    [Show full text]