Nootropics- Memory Boosters
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(12) United States Patent (10) Patent No.: US 8,148,546 B2 Schuster Et Al
US008148546B2 (12) United States Patent (10) Patent No.: US 8,148,546 B2 Schuster et al. (45) Date of Patent: Apr. 3, 2012 (54) TETRAHYDROCARBAZOLE DERIVATIVES (58) Field of Classification Search .................. 548/448: ASLGANDS OF G-PROTEIN COUPLED 51474 11 RECEPTORS See application file for complete search history. (75) Inventors: Tilmann Schuster, Grossostheim (DE); Klaus Paulini, Maintal (DE); Peter (56) References Cited Schmidt, Schoeneck (DE); Silke Baasner, Schoeneck (DE); Emmanuel FOREIGN PATENT DOCUMENTS Polymeropoulos, Frankfurt (DE); WO WO O3051837 * 6, 2003 Eckhard Guenther, Maintal (DE); WO WO 2006005484 * 1, 2006 Michael Teifel, Weiterstadt (DE) OTHER PUBLICATIONS (73) Assignee: AEterna Zentaris GmbH, Frankfurt Kubinyi (3D QSAR in Drug Design: Ligand-Protein Interactions and (DE) Molecular Similarity, vol. 2-3, Springer, 1998, 800 pages), TOC, pp. 243-244 provided.* *) NotOt1Ce: Subjubject to anyy d1Sclaimer,disclai theh term off thisthi Tatsuta et al. (Bioorg. Med. Chem. Lett. 15 (2005) 2265-2269).* patent is extended or adjusted under 35 Wermuth, The Practice of Medicinal Chemsitry, 2d ed. (2003), 768 U.S.C. 154(b) by 852 days. pages, chs. 9-10 provided.* CAPLUS Abstract of WO O3051837.* (21) Appl. No.: 12/109,479 * cited by examiner (22) Filed: Apr. 25, 2008 (65) Prior Publication Data Primary Examiner — Robert Havlin (74) Attorney, Agent, or Firm — Oblon, Spivak, US 2009/O 170783 A1 Jul. 2, 2009 McClelland, Maier & Neustadt, L.L.P. Related U.S. Application Data (60) Provisional application No. 60/914,424, filed on Apr. (57) ABSTRACT 27, 2007. The present invention provides novel tetrahydrocarbazole compounds according to formula (I) as ligands of G-protein (30) Foreign Application Priority Data coupled receptors (GPCR) which are useful in the treatment and/or prophylaxis of physiological and/or pathological con Apr. -
Yerevan State Medical University After M. Heratsi
YEREVAN STATE MEDICAL UNIVERSITY AFTER M. HERATSI DEPARTMENT OF PHARMACY Balasanyan M.G. Zhamharyan A.G. Afrikyan Sh. G. Khachaturyan M.S. Manjikyan A.P. MEDICINAL CHEMISTRY HANDOUT for the 3-rd-year pharmacy students (part 2) YEREVAN 2017 Analgesic Agents Agents that decrease pain are referred to as analgesics or as analgesics. Pain relieving agents are also called antinociceptives. An analgesic may be defined as a drug bringing about insensibility to pain without loss of consciousness. Pain has been classified into the following types: physiological, inflammatory, and neuropathic. Clearly, these all require different approaches to pain management. The three major classes of drugs used to manage pain are opioids, nonsteroidal anti-inflammatory agents, and non opioids with the central analgetic activity. Narcotic analgetics The prototype of opioids is Morphine. Morphine is obtained from opium, which is the partly dried latex from incised unripe capsules of Papaver somniferum. The opium contains a complex mixture of over 20 alkaloids. Two basic types of structures are recognized among the opium alkaloids, the phenanthrene (morphine) type and the benzylisoquinoline (papaverine) type (see structures), of which morphine, codeine, noscapine (narcotine), and papaverine are therapeutically the most important. The principle alkaloid in the mixture, and the one responsible for analgesic activity, is morphine. Morphine is an extremely complex molecule. In view of establish the structure a complicated molecule was to degrade the: compound into simpler molecules that were already known and could be identified. For example, the degradation of morphine with strong base produced methylamine, which established that there was an N-CH3 fragment in the molecule. -
(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. -
Modafinil and Modafinil Analogues: Free Radical Mechanism of the Eugeroic and Cognitive Enhancment Effect Clifford Fong
Modafinil and modafinil analogues: free radical mechanism of the eugeroic and cognitive enhancment effect Clifford Fong To cite this version: Clifford Fong. Modafinil and modafinil analogues: free radical mechanism of the eugeroic and cognitive enhancment effect. [Research Report] Eigenenergy. 2018. hal-01933737 HAL Id: hal-01933737 https://hal.archives-ouvertes.fr/hal-01933737 Submitted on 24 Nov 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Modafinil and modafinil analogues: free radical mechanism of the eugeroic and cognitive enhancment effect Clifford W. Fong Eigenenergy, Adelaide, South Australia. Keywords: Modafinil, modafinil-like analogues, eugeroic effect, cognitive enhancement, free radicals, quantum mechanics Abbreviations Dopamine DA, dopamine transporter DAT, Dissociative electron transfer or attachment DET, Linear free energy relationship LFER, free energy of water desolvation ΔG desolv,CDS , lipophilicity free energy ΔG lipo,CDS, cavity dispersion solvent structure of the first solvation shell CDS, highest occupied molecular orbital HOMO, lowest unoccupied molecular orbital LUMO, multiple correlation coefficient R 2, the F test of significance, standards errors for the estimate (SEE) and standard errors of the variables SE(ΔG desolCDS ), SE(ΔG lipoCDS ), SE(Dipole Moment), SE (Molecular Volume), transition state TS, reactive oxygen species ROS. -
Supplementary Digital Content REVIEW of ANXIETY MODELS USED in 2010-2011. Type of the Study. Here We Cathegorize the Study Accor
Supplementary digital content REVIEW OF ANXIETY MODELS USED IN 2010-2011. LEGEND Type of the study. Here we cathegorize the study according to its major aim or major finding as follows: anxiogenic effects, the compound had effects opposite to expectations; detection of anxiolytic effect, anxiolytic effects were noticed but no suggestion was formulated for use as anxiolytics; established anxiolytic, well-known anxiolytics studied for various reasons; no effect on anxiety, the compound did not fulfil expectations; mechanism, studies employing anxiolytic treatments but addressing developmental issues, neural mechanisms, drug interactions etc.; putative novel anxiolytic, the authors suggested the compound for anxiolytic drug development; (H), the tested compound was an herbal extract; (Ho), purified or synthesized compound of herbal origin. Anxiety tests. The tests listed in Table 1 were considered 'classical' for the reasons specified in the Abstract. Modifier. Tests are sometimes performed under unconventional conditions to induce heightened levels of anxiety and by this to icrease the translational value of the test. Procedures that altered (usually increased) anxiety levels normally shown in the given test were categorized as follows. chemical, hormonal or pharmacological treatments (e.g. ovarectomy, drug administration in adolescence, etc.); condition, modified testing conditions (e.g. high lighting, no habituation to the testing room, etc.); neural, treatments that affect neural functions (e.g. brain lesions, inhibited neurogenesis); selection, subjects from selection lines, specific strains, etc; stress, subjects exposed to stressors with long-lasting consequences (e.g. chronic immobility, drug withdrawal, etc); subject, the use of specific subjects classes (aged subjects, females, etc.); transgenic, the effects of drugs were studied in genetically engineered subjects. -
WO 2013/142184 Al 26 September 2013 (26.09.2013) P O P C T
(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 2013/142184 Al 26 September 2013 (26.09.2013) P O P C T (51) International Patent Classification: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, A61K 33/16 (2006.01) A61K 31/7048 (2006.01) HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, A61K 33/14 (2006.01) A61K 31/70 (2006.01) KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, A61K 33/18 (2006.01) A61K 31/4196 (2006.01) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, (21) International Application Number: RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, PCT/US20 13/030788 TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, (22) International Filing Date: ZM, ZW. 13 March 2013 (13.03.2013) (84) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (26) Publication Language: English UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (30) Priority Data: TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 61/612,689 19 March 2012 (19.03.2012) US EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (71) Applicant: YALE UNIVERSITY [US/US]; Two Whitney TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Avenue, New Haven, CT 065 10 (US). -
Plant-Mediated Enantioselective Transformation of Indan-1-One and Indan-1-Ol. Part 2
molecules Article Plant-Mediated Enantioselective Transformation of Indan-1-one and Indan-1-ol. Part 2 Wanda M ˛aczka 1,* , Katarzyna Wi ´nska 1,* , Małgorzata Grabarczyk 1,* and Renata Galek 2 1 Department of Chemistry, Wroclaw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroclaw, Poland 2 Department of Genetics, Plant Breeding and Seed Production, Wroclaw University of Environmental and Life Sciences Pl. Grunwaldzki 24A, 53-363 Wroclaw, Poland; [email protected] * Correspondence: [email protected] (W.M.); [email protected] (K.W.); [email protected] (M.G.); Tel.: +48-71-320-5213 (W.M. & K.W.) Received: 31 October 2019; Accepted: 25 November 2019; Published: 27 November 2019 Abstract: The main purpose of this publication was to obtain the S-enantiomer of indan-1-ol with high enantiomeric excess and satisfactory yield. In our research, we used carrot callus cultures (Daucus carota L.), whereby the enzymatic system reduced indan-1-one and oxidized indan-1-ol. During the reaction of reduction, after five days, we received over 50% conversion, with the enantiomeric excess of the formed S-alcohol above 99%. In turn, during the oxidation of racemic indan-1-ol after 15 days, 36.7% of alcohol with an enantiomeric excess 57.4% S(+) remained in the reaction mixture. In addition, our research confirmed that the reactions of reduction and oxidation are competing reactions during the transformation of indan-1-ol and indan-1-one in carrot callus cultures. Keywords: indan-1-one; indan-1-ol; biotransformation; reduction; oxidation; carrot; callus culture 1. -
Download Product Insert (PDF)
PRODUCT INFORMATION Semax Item No. 27719 CAS Registry No.: 80714-61-0 N Formal Name: L-methionyl-L-α-glutamyl- N H S L-histidyl-L-phenylalanyl-L- H2N prolylglycyl-L-proline O Synonym: ACTH4-7-PGP N H N N O MF: C37H51N9O10S O FW: 813.9 H N OH N O H Purity: ≥95% N O O O Supplied as: A solid H Storage: -20°C O HO Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures Semax is supplied as a solid. A stock solution may be made by dissolving the semax in the solvent of choice, which should be purged with an inert gas. Semax is soluble in organic solvents such as DMSO and dimethyl formamide. The solubility of semax in these solvents is approximately 5 and 1 mg/ml, respectively. Further dilutions of the stock solution into aqueous buffers or isotonic saline should be made prior to performing biological experiments. Ensure that the residual amount of organic solvent is insignificant, since organic solvents may have physiological effects at low concentrations. Organic solvent-free aqueous solutions of semax can be prepared by directly dissolving the solid in aqueous buffers. The solubility of semax in PBS, pH 7.2, is approximately 10 mg/ml. We do not recommend storing the aqueous solution for more than one day. Description Semax is a synthetic peptide analog of adrenocorticotropic hormone (ACTH) (4-10) (Item No. 27106) that has neuroprotective, analgesic, and anxiolytic properties.1-3 In vivo, semax (0.3 mg/kg) reduces cortical nitric oxide (NO) production and the number of neurological disturbances, such as seizures, falling, and twisting, in a rat model of global ischemia.1 It decreases acetic acid-induced writhing and nociception in a hind paw compression test in mice when administered at doses ranging from 0.015 to 0.5 mg/kg.2 Semax also increases time spent in the open arms in the elevated plus maze, indicating anxiolytic activity, in a rat model of maternal deprivation-induced anxiety.3 References 1. -
Effects of Semax on Dopaminergic and Serotoninergic Systems of the Brain K
Doklady Biological Sciences, Vol. 394, 2004, pp. 1–3. Translated from Doklady Akademii Nauk, Vol. 394, No. 1, 2004, pp. 130–132. Original Russian Text Copyright © 2004 by Eremin, Kudrin, Grivennikov, Miasoedov, Rayevsky. PHYSIOLOGY Effects of Semax on Dopaminergic and Serotoninergic Systems of the Brain K. O. Eremin*, V. S. Kudrin*, I. A. Grivennikov**, Academician N. F. Miasoedov**, and K. S. Rayevsky* Received June 11, 2003 Short-term effects of the synthetic nootropic peptide in rats and simultaneously raises the intracellular level Semax on the content and metabolism of monoamines of dopamine in the striatum [6]. in the brain of C57/Bl6 mice and Sprague–Dawley rats The goal of this study was to examine the effects of were studied. Intraperitoneal injection of Semax at a Semax on the neurochemical parameters of the dopam- dose of 0.15 mg/kg caused an increase in the tissue con- inergic and serotoninergic systems of the animal brain. centrations of 5-hydroxyindoleacetic acid (5-HIAA) in Semax was administered at a dose of 0.15 mg per kilo- the hypothalamus and striatum of mice 0.5 and 2 h after gram body weight to ë57/Bl6 mice, and their hypothal- the injection. Using brain microdialysis, we detected amus and striatum were analyzed for tissue levels of increased levels of extracellular 5-HIAA in the striatum dopamine (DA) and its metabolites 3,4-dihydroxyphe- of freely moving rats 1 h after administration of 0.15 or nylacetic acid (DOPAC) and homovanillic acid (HVA), 0.6 mg/kg Semax. The effect lasted for an additional as well as serotonin (or 5-hydroxytriptamine, 5-HT) 3 h. -
Screening of 109 Neuropeptides on Asics Reveals No Direct Agonists
www.nature.com/scientificreports OPEN Screening of 109 neuropeptides on ASICs reveals no direct agonists and dynorphin A, YFMRFamide and Received: 7 August 2018 Accepted: 14 November 2018 endomorphin-1 as modulators Published: xx xx xxxx Anna Vyvers, Axel Schmidt, Dominik Wiemuth & Stefan Gründer Acid-sensing ion channels (ASICs) belong to the DEG/ENaC gene family. While ASIC1a, ASIC1b and ASIC3 are activated by extracellular protons, ASIC4 and the closely related bile acid-sensitive ion channel (BASIC or ASIC5) are orphan receptors. Neuropeptides are important modulators of ASICs. Moreover, related DEG/ENaCs are directly activated by neuropeptides, rendering neuropeptides interesting ligands of ASICs. Here, we performed an unbiased screen of 109 short neuropeptides (<20 amino acids) on fve homomeric ASICs: ASIC1a, ASIC1b, ASIC3, ASIC4 and BASIC. This screen revealed no direct agonist of any ASIC but three modulators. First, dynorphin A as a modulator of ASIC1a, which increased currents of partially desensitized channels; second, YFMRFamide as a modulator of ASIC1b and ASIC3, which decreased currents of ASIC1b and slowed desensitization of ASIC1b and ASIC3; and, third, endomorphin-1 as a modulator of ASIC3, which also slowed desensitization. With the exception of YFMRFamide, which, however, is not a mammalian neuropeptide, we identifed no new modulator of ASICs. In summary, our screen confrmed some known peptide modulators of ASICs but identifed no new peptide ligands of ASICs, suggesting that most short peptides acting as ligands of ASICs are already known. Acid-sensing ion channels form a small family of proton-gated ion channels that belongs to the degenerin/epi- thelial Na+ channel (DEG/ENaC) gene family1. -
1St ANNUAL UNDERGRADUATE RESEARCH SYMPOSIUM
Table of Contents Entree Subject Page 1 History of the Symposium 2 2 Program Schedule 4 3 Poster Abstract 28 4 Author/Faculty Information 132 5 Participating Institutions 137 1 HISTORY OF THE SYMPOSIUM Few activities are as rewarding as research to the motivated students as well as faculty mentors. In addition to the acquisition of invaluable research skills, students learn how knowledge is created and experience the excitement of the “eureka moment”. To celebrate undergraduate achievements, a research symposium has been held since 2007 on WPUNJ campus for students in biological and chemical sciences. In this event, undergraduate students present and display their research and creative work to the university and the scientific community from the Tri state area. This symposium provides an opportunity to the students to showcase their talents and share their research achievements with their peers from about twenty universities from Tri state area. The students and faculty from different universities as well as staff, and community members of WPU are invited to explore the latest in undergraduate research. Featured events include the poster presentation and Awards ceremony. The Symposium also features a keynote lecture by a distinguished researcher. 2 SYMPOSIUM ORGANIZING COMMITTEE Organizers Dr. Jaishri Menon Dr. Bhanu P. S. Chauhan Committee Members Dr. Jean Fuller-Stanley Dr. Michael Peek Dr. Eileen Gardner Dr. Jeung Woon Lee Dr. Carey Waldburger Dr. Pradeep Patnaik Dr. Mihaela Jitianu Dr. Mukesh Sahni Ms. Karyn Lapadura 3 SCHEDULE OF EVENTS 8:00 a.m. – 9:00 a.m. Registration & Breakfast Ballroom 9:00 a.m. – 9:15 am Welcome and Opening Remarks Dr. -
Les Antidépresseurs De La Performance
Annales de Toxicologie Analytique, vol. XII, n° 1, 2000 Les antidépresseurs de la performance Performance antidepressant drugs Jean-Pierre GOULLÉ*, Christian LACROIX Laboratoire de Pharmacocinétique et de Toxicologie Clinique, Groupe Hospitalier BP 24 - 76083 LE HAVRE Cedex - Tel : 02 32 73 32 18 - Fax : 02 32 73 32 38 * Auteur à qui adresser la correspondance : Docteur Jean-Pierre GOULLÉ, Laboratoire de Pharmacocinétique et de Toxicologie Clinique, Groupe Hospitalier, Jacques Monod - BP 24 - 76083 LE HAVRE Tel : 02 32 73 32 23 - Fax : 02 32 73 32 38 (Reçu le 17 décembre 1999 ; accepté le 15 janvier 2000) RÉSUMÉ SUMMARY En France, au cours de la période 1991-1997, alors que la Whereas in France the sale of psychotropic medication vente des médicaments psychotropes a augmenté de 7 %, le increased 7 % in the period between 1991 and 1997, the marché des antidépresseurs s'est littéralement envolé avec antidepressant drugs market literally exploded with a pro• une progression de plus de 40 %. Cette consommation, 2 à 3 gression of 40 %. This consumption 2 to 3 times greater than fois plus importante que celle de nos voisins européens, est that of our European neighbours created an abuse which génératrice d'abus conduisant à une accoutumance, à une lead to habituation, to an addiction, and even to drug abuse. assuétude, voire à une véritable conduite toxicophile. Les Antidepressant drugs (AD) pertain to the substances which antidépresseurs (AD) font partie des substances qui sont uti• are used by man to improve its performance due to its phar• lisées par l'homme pour améliorer sa performance, en rai• macological effects.