DOCSLIB.ORG

WO 2014/115152 Al 31 July 20 14 (31.07.2014) W P O P CT

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WO 2014/115152 Al 31 July 20 14 (31.07.2014) W P O P CT (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2014/115152 Al 31 July 20 14 (31.07.2014) W P O P CT (51) International Patent Classification: (72) Inventor; and A61K 51/04 (2006.01) (71) Applicant (for PG only): BEN-HAIM, Shlomo [IL/CH]; c/o Lemuria Alliance SA, 17 Rue des Pierres-du-Niton, (21) International Application Number: CH- 1207 Geneva (CH). PCT/IL20 14/050090 (74) Agents: G.E. EHRLICH (1995) LTD. et al: 11 Mena- (22) International Filing Date: chem Begin Road, 5268104 Ramat Gan (IL). 24 January 2014 (24.01 .2014) (81) Designated States (unless otherwise indicated, for every English (25) Filing Language: kind of national protection available): AE, AG, AL, AM, (26) Publication Language: English AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (30) Priority Data: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, 61/756,1 12 24 January 2013 (24.01. 2013) US HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 61/776,599 11 March 2013 ( 11.03 2013) US KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, 61/803,61 1 20 March 2013 (20.03 2013) us MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 61/83 1,664 6 June 2013 (06.06 2013) us OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 61/875,069 ! September 2013 (08.09. 2013) us SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, 61/875,074 ! September 2013 (08.09. 2013) us TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, 61/875,070 ! September 2013 (08.09. 2013) us ZW. 61/925,670 10 January 2014 (10.01. 2014) us 61/925,669 10 January 2014 (10.01. 2014) us (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant for all designated States except PG) : TYLER- GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, TON INTERNATIONAL HOLDINGS INC.; Jayla UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, Place, Wickhams Cay 1, Road Town (VG). TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, [Continued on nextpage] (54) Title: NEURONAL IMAGING AND TREATMENT (57) Abstract: A method is disclosed herein for imaging at least one autonomic nervous system synaptic center in a subject, as well as a method of diagnosing and/or monitoring a medical con dition or disease associated with an autonomic nervous system, and a method of guiding a ther apy of such a medical condition or disease. The methods comprise administering to the subject a radioactive tracer which selectively binds to autonomic nervous system synapses; measuring radioactive emission of the tracer to obtain data describing a distribution of the tracer in the body; and analyzing the data in order to identify at least one region exhibiting a high concentra > tion of the tracer. Further disclosed herein are radioactive tracers, uses thereof, and an apparat us, for use in a method disclosed herein. EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, Published: LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, — with international search report (Art. 21(3)) SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: — of inventorship (Rule 4.17(iv)) NEURONAL IMAGING AND TREATMENT RELATED APPLICATIONS: This application claims the benefit of priority of U.S. Provisional Patent Application No. 61/756,112, filed January 24, 2013, U.S. Provisional Patent Application No. 61/776,599, filed March 11, 2013, U.S. Provisional Patent Application No. 61/803,611 filed March 20, 2013, U.S. Provisional Patent Application No. 61/831,664, filed June 6, 2013, U.S. Provisional Patent Application Nos. 61/875,069, 61/875,070 and 61/875,074, filed September 8, 2013, and U.S. Provisional Patent Application Nos. 61/925,669 and 61/925,670, filed January 10, 2014, the contents of which are incorporated herein by reference in their entirety. FIELD AND BACKGROUND OF THE INVENTION The present invention, in some embodiments thereof, relates to methods and systems of imaging and, more particularly, but not exclusively, to methods and systems of medical imaging using a radioactive tracer with affinity to nervous tissue. The autonomic nervous system (ANS) is a part of the peripheral nervous system that controls, usually at an unconscious level, various bodily functions such as heart rate, vasomotor activity, digestion, respiration, reflex actions and the like. The ANS is regulated by the medulla oblongata and hypothalamus in the brain. ANS functions include afferent (sensory) activity - transmitting signals from the viscera to the central nervous system (CNS), as well as efferent (motor) activity - transmitting signals from the CNS to the periphery. Efferent activity in the ANS is typically divided into two divisions, the sympathetic nervous system and the parasympathetic nervous system. To a considerable degree, these divisions act in parallel to one another, and often have opposing effects. The sympathetic division is usually associated with mobilization of a quick response, whereas the parasympathetic division is usually associated with lower activities. The peripheral nervous system also includes the somatic nervous system (SoNS), which controls voluntary movements via efferent neurons and conducts, via afferent neurons, impulses of pain, touch and temperature from the body surface, and muscle, tendon and joint sense from within the body. Afferent (sensory) neurons of the ANS and SoNS extend from peripheral organs to synapses in the spinal cord. Cell bodies of afferent neurons are aggregated in spinal ganglia, just outside the spinal cord. Efferent SoNS neurons are located in the spinal cord and extend to synapses at neuromuscular junctions at the innervated muscle. In contrast to afferent and SoNS efferent activity, ANS efferent innervation is characterized by the involvement of two sequential efferent neurons which communicate via a synapse in a ganglion. The preganglionic neuron carries a signal from the central nervous system to the ganglion, and the postganglionic neuron carries a signal from the ganglion to the target (e.g., an innervated organ). Sympathetic ganglia include the paravertebral ganglia, which are located along the spine, prevertebral ganglia, which are located in the abdomen and innervate abdominal organs, and the adrenal medulla in the adrenal gland, which is a modified ganglion in which the postganglionic cells release hormones into the blood instead of acting as neurons. In comparison to sympathetic ganglia, parasympathetic ganglia are usually small and located close to the organ they innervate, that is, the postganglionic neurons are relatively short. Acetylcholine is the primary neurotransmitter secreted at synapses by sympathetic and parasympathetic preganglionic neurons in ganglia, by SoNS neurons and parasympathetic postganglionic neurons at innervated organs, and by sympathetic postganglionic neurons at sweat glands. Acetylcholine receptors in ANS ganglia and neuromuscular junctions are typically nicotinic receptors, and acetylcholine receptors at ANS synapses in innervated organs are typically muscarinic receptors. In contrast, sympathetic postganglionic neurons generally secrete adrenergic neurotransmitters, primarily norepinephrine (noradrenaline). The sympathetic and parasympathetic nervous systems are not entirely separate. For example, cardiac ganglia, typically considered as part of the parasympathetic nervous system, also include adrenergic synapses of sympathetic neurons, which provide input to parasympathetic postganglionic neurons, and a similar sympathetic input to parasympathetic postganglionic neurons occurs in pelvic prevertebral ganglia [Smith, Am J Physiol 1999, 276:R455-R467; Arora et al., Anat Rec A Discov Mol Cell Evol Biol 2003, 271:249-258]. Atrial fibrillation may be treated by ablation or surgery aimed at disrupting autonomic signaling to atria, as both sympathetic and parasympathetic stimuli appear to be involved in atrial fibrillation. Neurons around the pulmonary veins, and the nearby cardiac ganglionated plexuses, have been reported to be effective targets for ablation and/or surgery [Arora, Circ Arrhythm Electrophysiol 2012, 5:850-859; Tan et al., Heart Rhythm 2007, 4:S57-S60]. A variety of medical imaging techniques are available for obtaining images of internal organs. Techniques such as X-ray computerized tomography (CT), magnetic resonance imaging (MRI), and ultrasound scans utilize an external source of irradiation; whereas techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) utilize nuclear radiation emitted by a radioactive tracer within the body. In such techniques, data may be obtained in a manner which provides 3- dimensional information, such that the data can be processed so as to generate a volumetric image. Orbiting detectors from multiple directions may be used to generate a volumetric image by computed tomography. PET and SPECT use a collimator to allow only radiation from a certain direction to reach the detector. Typically, this collimator is constructed to provide a multiplicity of small holes in a dense, high-atomic number material such as lead or tungsten. Radiation will pass through a hole if it travels in a direction aligned with a hole but will tend to be absorbed by the collimator material if it travels in a different direction. Radioactive tracers may be selected so as to allow for selective imaging of a particular tissue type or activity. Langer & Haldin [Eur J Nucl Med 2002, 29:416-434] describe PET and SPECT radioactive tracers for mapping the cardiac nervous system, including catecholamines and catecholamine analogs such as mlBG (m-iodobenzylguanidine) and - hydroxyephedrine for imaging adrenergic synapses, and vesamicol derivatives for imaging cholinergic synapses.
Load more

Recommended publications
  • Synthesis and Characterization of in Vitro and in Vivo Profiles of Hydroxybupropion Analogues: Aids to Smoking Cessation
    Barrow Neurological Institute at St. Joseph's Hospital and Medical Center Barrow - St. Joseph's Scholarly Commons Neurobiology 6-24-2010 Synthesis And Characterization Of In Vitro And In Vivo Profiles Of Hydroxybupropion Analogues: Aids To Smoking Cessation Ronald J. Lukas Barrow Neurological Institute, [email protected] Ana Z. Muresan M. Imad Damaj Bruce E. Blough Xiaodong Huang See next page for additional authors Follow this and additional works at: https://scholar.barrowneuro.org/neurobiology Recommended Citation Lukas, Ronald J.; Muresan, Ana Z.; Damaj, M. Imad; Blough, Bruce E.; Huang, Xiaodong; Navarro, Hernan A.; Mascarella, S. Wayne; Eaton, J. Brek; Marxer-Miller, Syndia K.; and Carroll, F. Ivy, "Synthesis And Characterization Of In Vitro And In Vivo Profiles Of Hydroxybupropion Analogues: Aids To Smoking Cessation" (2010). Neurobiology. 280. https://scholar.barrowneuro.org/neurobiology/280 This Article is brought to you for free and open access by Barrow - St. Joseph's Scholarly Commons. It has been accepted for inclusion in Neurobiology by an authorized administrator of Barrow - St. Joseph's Scholarly Commons. For more information, please contact [email protected], [email protected]. Authors Ronald J. Lukas, Ana Z. Muresan, M. Imad Damaj, Bruce E. Blough, Xiaodong Huang, Hernan A. Navarro, S. Wayne Mascarella, J. Brek Eaton, Syndia K. Marxer-Miller, and F. Ivy Carroll This article is available at Barrow - St. Joseph's Scholarly Commons: https://scholar.barrowneuro.org/neurobiology/ 280 J. Med. Chem. 2010, 53, 4731–4748 4731 DOI: 10.1021/jm1003232 Synthesis and Characterization of in Vitro and in Vivo Profiles of Hydroxybupropion Analogues: Aids to Smoking Cessation Ronald J.
    [Show full text]
  • Implications in the Management of Depression and Anxiety
    Journal name: Neuropsychiatric Disease and Treatment Article Designation: Review Year: 2016 Volume: 12 Neuropsychiatric Disease and Treatment Dovepress Running head verso: Montoya et al Running head recto: Noradrenergic paradox in depression and anxiety open access to scientific and medical research DOI: http://dx.doi.org/10.2147/NDT.S91311 Open Access Full Text Article REVIEW The noradrenergic paradox: implications in the management of depression and anxiety Alonso Montoya1 Abstract: Both major depressive disorder and the anxiety disorders are major causes of disability Robert Bruins1 and markedly contribute to a significant global burden of the disease worldwide. In part because Martin A Katzman2 of the significant socioeconomic burden associated with these disorders, theories have been devel- Pierre Blier3 oped to specifically build clinical treatment approaches. One such theory, the monoaminergic hypothesis, has led to the development of several generations of selective and nonselective inhibi- 1Eli Lilly Canada Inc, 2START Clinic for the Mood and Anxiety Disorders, tors of transporters of serotonin and norepinephrine, with the goal of augmenting monoaminergic Toronto, 3Mood Disorders Research transmission. These efforts have led to considerable success in the development of antidepressant Unit, Institute of Mental Health therapeutics. However, there is a strong correlation between enhanced noradrenergic activity Research, University of Ottawa, Ottawa, ON, Canada and fear and anxiety. Consequently, some physicians have expressed concerns that the same enhanced noradrenergic activity that alleviates depression could also promote anxiety. The fact that the serotonergic and noradrenergic reuptake inhibitors are successfully used in the treatment For personal use only. of anxiety and panic disorders seems paradoxical. This review was undertaken to determine if any clinical evidence exists to show that serotonergic and noradrenergic reuptake inhibitors can cause anxiety.
    [Show full text]
  • PRODUCT INFORMATION ABT-594 Item No
    PRODUCT INFORMATION ABT-594 Item No. 22822 CAS Registry No.: 203564-54-9 Formal Name: 5-[(2R)-2-azetidinylmethoxy]-2- H chloro-pyridine, monohydrochloride N Synonyms: Ebanicline, Tebanicline O MF: C9H11ClN2O • HCl FW: 235.1 N Purity: ≥95% Cl Supplied as: A solid • HCl Storage: -20°C Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures ABT-594 is supplied as a solid. A stock solution may be made by dissolving the ABT-594 in the solvent of choice. ABT-594 is soluble in the organic solvent DMSO, which should be purged with an inert gas. Description ABT-594 is a potent agonist of neuronal α4β2 subunit-containing nicotinic acetylcholine receptors 1 (nAChRs; Ki = 37 pM in a radioligand binding assay). It is selective for neuronal nAChRs over neuromuscular α1β1δγ subunit-containing nAChRs (Ki = 10,000 nM), α1B-, α2B-, and α2C-adrenergic receptors (Kis = 890, 597, and 342 nM, respectively), and 70 other receptors, enzymes, and transporters 86 + (Kis = >1,000 nM) in radioligand binding assays. ABT-594 induces [ Rb ] efflux in K177 cells transfected with human neuronal α4β2 subunit-containing nAChRs (EC50 = 140 nM). In vivo, ABT-594 (0.05 and 0.01 mg/kg, s.c.) increases latency to paw withdrawal in a hot-plate test in rats.2 It also induces hypothermia, seizures, and an increase in blood pressure. References 1. Donnelly-Roberts, D.L., Puttfarcken, P.S., Kuntzweiler, T.A., et al. ABT-594 [(R)-5-(2-azetidinylmethoxy)- 2-chloropyridine]: A novel, orally effective analgesic acting via neuronal nicotinic acetylcholine receptors: I.
    [Show full text]
  • In Silico Methods for Drug Repositioning and Drug-Drug Interaction Prediction
    In silico Methods for Drug Repositioning and Drug-Drug Interaction Prediction Pathima Nusrath Hameed ORCID: 0000-0002-8118-9823 Submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy Department of Mechanical Engineering THE UNIVERSITY OF MELBOURNE May 2018 Copyright © 2018 Pathima Nusrath Hameed All rights reserved. No part of the publication may be reproduced in any form by print, photoprint, microfilm or any other means without written permission from the author. Abstract Drug repositioning and drug-drug interaction (DDI) prediction are two fundamental ap- plications having a large impact on drug development and clinical care. Drug reposi- tioning aims to identify new uses for existing drugs. Moreover, understanding harmful DDIs is essential to enhance the effects of clinical care. Exploring both therapeutic uses and adverse effects of drugs or a pair of drugs have significant benefits in pharmacology. The use of computational methods to support drug repositioning and DDI prediction en- able improvements in the speed of drug development compared to in vivo and in vitro methods. This thesis investigates the consequences of employing a representative training sam- ple in achieving better performance for DDI classification. The Positive-Unlabeled Learn- ing method introduced in this thesis aims to employ representative positives as well as reliable negatives to train the binary classifier for inferring potential DDIs. Moreover, it explores the importance of a finer-grained similarity metric to represent the pairwise drug similarities. Drug repositioning can be approached by new indication detection. In this study, Anatomical Therapeutic Chemical (ATC) classification is used as the primary source to determine the indications/therapeutic uses of drugs for drug repositioning.
    [Show full text]
  • The In¯Uence of Medication on Erectile Function
    International Journal of Impotence Research (1997) 9, 17±26 ß 1997 Stockton Press All rights reserved 0955-9930/97 $12.00 The in¯uence of medication on erectile function W Meinhardt1, RF Kropman2, P Vermeij3, AAB Lycklama aÁ Nijeholt4 and J Zwartendijk4 1Department of Urology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; 2Department of Urology, Leyenburg Hospital, Leyweg 275, 2545 CH The Hague, The Netherlands; 3Pharmacy; and 4Department of Urology, Leiden University Hospital, P.O. Box 9600, 2300 RC Leiden, The Netherlands Keywords: impotence; side-effect; antipsychotic; antihypertensive; physiology; erectile function Introduction stopped their antihypertensive treatment over a ®ve year period, because of side-effects on sexual function.5 In the drug registration procedures sexual Several physiological mechanisms are involved in function is not a major issue. This means that erectile function. A negative in¯uence of prescrip- knowledge of the problem is mainly dependent on tion-drugs on these mechanisms will not always case reports and the lists from side effect registries.6±8 come to the attention of the clinician, whereas a Another way of looking at the problem is drug causing priapism will rarely escape the atten- combining available data on mechanisms of action tion. of drugs with the knowledge of the physiological When erectile function is in¯uenced in a negative mechanisms involved in erectile function. The way compensation may occur. For example, age- advantage of this approach is that remedies may related penile sensory disorders may be compen- evolve from it. sated for by extra stimulation.1 Diminished in¯ux of In this paper we will discuss the subject in the blood will lead to a slower onset of the erection, but following order: may be accepted.
    [Show full text]
  • (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]
  • Axsome Therapeutics Enters Into Exclusive License Agreement with Pfizer Inc
    Axsome Therapeutics Enters into Exclusive License Agreement with Pfizer Inc. for Pfizer’s Reboxetine Clinical and Nonclinical Data and for New Phase 3 Esreboxetine Product Candidate Agreement accelerates ongoing clinical development of AXS-12 (reboxetine) in narcolepsy Expands Axsome’s pipeline with new Phase 3-stage esreboxetine product candidate for fibromyalgia Esreboxetine met primary endpoints in completed Pfizer Phase 3 and Phase 2 placebo-controlled clinical trials in fibromyalgia (p<0.001, and p<0.001) Pfizer to receive $11 million in Axsome stock and upfront cash, and up to $323 million in regulatory and sales milestones Company to host conference call today at 8:30 AM ET NEW YORK, January 13, 2020 (Globe Newswire) – Axsome Therapeutics, Inc. (NASDAQ: AXSM), a clinical- stage biopharmaceutical company developing novel therapies for the management of central nervous system (CNS) disorders, has entered into an agreement with Pfizer Inc. (NYSE: PFE) for an exclusive U.S. license to Pfizer’s clinical and nonclinical data, and intellectual property for reboxetine, the active pharmaceutical ingredient in AXS-12 which Axsome is developing for the treatment of narcolepsy. The agreement also provides Axsome exclusive rights to develop and commercialize esreboxetine, a new late-stage product candidate now referred to as AXS-14, in the U.S. for the treatment of fibromyalgia. Under the terms of the agreement, Axsome will receive from Pfizer an exclusive U.S. license to Pfizer data for reboxetine and esreboxetine encompassing a full range of nonclinical studies, and short-term and long-term clinical trials involving more than five thousand patients. The licensed data includes results from a positive Phase 3 and a positive Phase 2 trial of esreboxetine in the treatment of fibromyalgia.
    [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]
  • NINDS Custom Collection II
    ACACETIN ACEBUTOLOL HYDROCHLORIDE ACECLIDINE HYDROCHLORIDE ACEMETACIN ACETAMINOPHEN ACETAMINOSALOL ACETANILIDE ACETARSOL ACETAZOLAMIDE ACETOHYDROXAMIC ACID ACETRIAZOIC ACID ACETYL TYROSINE ETHYL ESTER ACETYLCARNITINE ACETYLCHOLINE ACETYLCYSTEINE ACETYLGLUCOSAMINE ACETYLGLUTAMIC ACID ACETYL-L-LEUCINE ACETYLPHENYLALANINE ACETYLSEROTONIN ACETYLTRYPTOPHAN ACEXAMIC ACID ACIVICIN ACLACINOMYCIN A1 ACONITINE ACRIFLAVINIUM HYDROCHLORIDE ACRISORCIN ACTINONIN ACYCLOVIR ADENOSINE PHOSPHATE ADENOSINE ADRENALINE BITARTRATE AESCULIN AJMALINE AKLAVINE HYDROCHLORIDE ALANYL-dl-LEUCINE ALANYL-dl-PHENYLALANINE ALAPROCLATE ALBENDAZOLE ALBUTEROL ALEXIDINE HYDROCHLORIDE ALLANTOIN ALLOPURINOL ALMOTRIPTAN ALOIN ALPRENOLOL ALTRETAMINE ALVERINE CITRATE AMANTADINE HYDROCHLORIDE AMBROXOL HYDROCHLORIDE AMCINONIDE AMIKACIN SULFATE AMILORIDE HYDROCHLORIDE 3-AMINOBENZAMIDE gamma-AMINOBUTYRIC ACID AMINOCAPROIC ACID N- (2-AMINOETHYL)-4-CHLOROBENZAMIDE (RO-16-6491) AMINOGLUTETHIMIDE AMINOHIPPURIC ACID AMINOHYDROXYBUTYRIC ACID AMINOLEVULINIC ACID HYDROCHLORIDE AMINOPHENAZONE 3-AMINOPROPANESULPHONIC ACID AMINOPYRIDINE 9-AMINO-1,2,3,4-TETRAHYDROACRIDINE HYDROCHLORIDE AMINOTHIAZOLE AMIODARONE HYDROCHLORIDE AMIPRILOSE AMITRIPTYLINE HYDROCHLORIDE AMLODIPINE BESYLATE AMODIAQUINE DIHYDROCHLORIDE AMOXEPINE AMOXICILLIN AMPICILLIN SODIUM AMPROLIUM AMRINONE AMYGDALIN ANABASAMINE HYDROCHLORIDE ANABASINE HYDROCHLORIDE ANCITABINE HYDROCHLORIDE ANDROSTERONE SODIUM SULFATE ANIRACETAM ANISINDIONE ANISODAMINE ANISOMYCIN ANTAZOLINE PHOSPHATE ANTHRALIN ANTIMYCIN A (A1 shown) ANTIPYRINE APHYLLIC
    [Show full text]
  • The Impact of Anaesthesia Protocols on BOLD Fmri Validity in Laboratory Rodents –A Systematic Review
    Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2019 The impact of anaesthesia protocols on BOLD fMRI validity in laboratory rodents –a systematic review Steiner, Aline Rebecca Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-175731 Dissertation Published Version Originally published at: Steiner, Aline Rebecca. The impact of anaesthesia protocols on BOLD fMRI validity in laboratory rodents –a systematic review. 2019, University of Zurich, Vetsuisse Faculty. Departement für klinische Diagnostik und Services, Abteilung für Anästhesiologie der Vetsuisse-Fakultät Universität Zürich Vorsteherin Departement: Prof. Dr. med. vet. FVH Regina Hofmann-Lehmann Leiterin Abteilung: Prof. Dr. med. vet. PhD, Dipl. ECVAA Regula Bettschart-Wolfensberger The Impact of Anaesthesia Protocols on BOLD fMRI Validity in Laboratory Rodents – a Systematic Review Inaugural-Dissertation zur Erlangung der Doktorwürde der Vetsuisse-Fakultät Universität Zürich vorgelegt von Aline Rebecca Steiner Tierärztin von Frutigen, Bern genehmigt auf Antrag von Prof. Dr. med. vet. PhD, Dipl. ECVAA Regula Bettschart-Wolfensberger, Referentin Dr. med. vet., Dipl. ECVPH Sonja Hartnack, Co-Referentin 2019 Table of Contents Table of Contents ..................................................................................................... 3 Abstract ....................................................................................................................
    [Show full text]
  • Efforts Towards the Synthesis of Epibatidine By: Marianne Hanna
    Efforts Towards the Synthesis of Epibatidine By: Marianne Hanna (Junior-Biochemistry major) Faculty Advisor: Dr. Thomas Montgomery Duquesne University- Bayer School of Natural Sciences 1 Abstract: Epibatidine is a naturally toxic chemical found in the secretion of poison dart frogs. Given its structural similarities to the compound nicotine epibatidine binds strongly to nicotine receptors in the central nervous system (CTS). Epibatidine’s bioactivity arises from its unique geometry which allows it to bind to the α4β2 subunit in the nicotinic receptor. This triggers an analgesic effect without a release of dopamine, differentiating its activity from opioids. Prior efforts towards synthesizing epibatidine and its analogs have involved many steps making them untenable for pharmaceutical use. By using computational and experimental methods to study the mechanism for an interrupted Polonovski [3+2] cycloaddition which will give direct access to the epibatidine core motif. By synthesizing strategic derivatives of epibatidine through this route we will investigate opioid alternatives which lack many of their addictive qualities. Background: Epibatidine is a toxic alkaloid that is isolated from the skin of poison dart tree frog Epipedobates tricolor, secretions from the frog are used by indigenous tribes in darts for hunting.1 The chemical structure was established in 1992 using NMR spectroscopy (proton NMR).2 Epibatidine possesses significant medicinal properties, it functions as an analgesic agent by binding to the nicotinic acetylcholine receptors (nAChRs) instead of the opioid receptors.3 Moreover it displays an affinity for said receptors that is 100- to 200-fold higher than nicotine. The alkaloid interacts with Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels and are expressed central and peripherally.
    [Show full text]
  • Cognitive, Behavioral, and Physiologic Responses John T
    Combined Nicotinic and Muscarinic Blockade in Elderly Normal Volunteers: Cognitive, Behavioral, and Physiologic Responses John T. Little, M.D., Douglas N. Johnson, Ph.D., Marcia Minichiello, M.A., Herb Weingartner, Ph.D., and Trey Sunderland, M.D. Establishing a pharmacologic model of the memory deficits scopolamine alone. Increased impairment was also seen for of Alzheimer’s disease could be an important tool in the mecamylamine 1 scopolamine condition as compared to understanding how memory fails. We examined the scopolamine alone in selected behavioral ratings. Pupil size combined effects of the muscarinic antagonist scopolamine increased when mecamylamine was added to scopolamine, and the nicotinic antagonist mecamylamine in eight normal while systolic blood pressure and pulse changed in elderly volunteers (age 61.9 6 8.3 yrs, SD). Each received concordance with ganglionic blockade. These data together four separate drug challenges (scopolamine (0.4 mg IV), with previous brain-imaging results suggest that this mecamylamine (0.2 mg/kg up to 15 mg PO), muscarinic–nicotinic drug combination may better model mecamylamine 1 scopolamine, and placebo). There was a Alzheimer’s disease than either drug alone. trend toward increased impairment in explicit memory for [Neuropsychopharmacology 19:60–69, 1998] the mecamylamine 1 scopolamine condition as compared to Published by Elsevier Science Inc. KEY WORDS: Scopolamine; Mecamylamine; Cognitive; al. 1985; Shimohama et al. 1986; Whitehouse and Au Geriatrics; Muscarinic antagonist; Nicotinic antagonist 1986; D’Amato et al. 1987; Zubenko et al. 1988), many cognitive dysfunction modeling studies have focused Given the limited animal models of Alzheimer’s disease on this system (Beatty et al.
    [Show full text]