Development of Novel Nicotinic Receptor
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Roger Lee Papke Box 100267 JHM Health Science Center Gainesville, Florida 32610
CURRICULUM VITAE Roger Lee Papke DEPARTMENT OF PHARMACOLOGY AND THERAPEUTICS UNIVERSITY OF FLORIDA SCHOOL OF MEDICINE Box 100267 J.H.M. Health Science Center Gainesville, Florida 32610 (352) 392-4712, FAX (352) 392-9696 [email protected] BIOGRAPHICAL DATA: Born: October 12, 1953, Kenmore, New York Married: December 24, 1980 to Clare Stokes Citizenship: U. S. A. EDUCATION: Starpoint Central School Pendleton, N. Y. Primary and Secondary N.Y.S. Regents Diploma 1971 New York University Washington Square College of Arts and Sciences 1971 - 1975 Majors in Biology and Classical Civilization Bachelor of Arts awarded May 1975 New York University Graduate school of Arts and Sciences 1975 - 1976 Thesis advisor: Dr. Fleur L. Strand Thesis title: An Alpha Adrenergic Response of Cardiac Muscle at an Alkaline pH Master of Science awarded May 1976 Cornell University Graduate School of Arts and Science 1976-1979: Section of Physiology Graduate Research Assistant in Reproductive Physiology Advisor: Dr. William Hansel Research topic: The endocrine control of delayed implantation in mink Cornell University Graduate School of Arts and Science 1979-1986: Section of Neurobiology and Behavior Thesis Advisor: Dr. Robert Oswald Primary research topic: Pharmacology of nicotinic acetylcholine receptors Thesis Title: The Gating of Single Channel Currents Through the Nicotinic Acetylcholine Receptors of BC3H-1 Cells: Effects of Agonists and Allosteric Ligands Ph.D. conferred January 1987 ACADEMIC APPOINTMENTS: 1987 Postdoctoral Research Associate: Department of Pharmacology, -
Differential Effects of Alkaloids on Memory in Rodents
www.nature.com/scientificreports OPEN Diferential efects of alkaloids on memory in rodents Patrick M. Callahan1,2, Alvin V. Terry Jr.1,2, Manuel C. Peitsch3, Julia Hoeng3* & Kyoko Koshibu3* Nicotinic acetylcholine receptors (nAChRs) play a critical role in the neuropharmacology of learning and memory. As such, naturally occurring alkaloids that regulate nAChR activity have gained interest for understanding and potentially improving memory function. In this study, we tested the acute efects of three known nicotinic alkaloids, nicotine, cotinine, and anatabine, in suppressing scopolamine-induced memory defcit in rodents by using two classic memory paradigms, Y-maze and novel object recognition (NOR) in mice and rats, respectively. We found that all compounds were able to suppress scopolamine-induced spatial memory defcit in the Y-maze spontaneous alternation paradigm. However, only nicotine was able to suppress the short-term object memory defcit in NOR, despite the higher doses of cotinine and anatabine used to account for their potential diferences in nAChR activity. These results indicate that cotinine and anatabine can uniquely regulate short-term spatial memory, while nicotine seems to have more robust and general role in memory regulation in rodents. Thus, nAChR-activating alkaloids may possess distinct procognitive properties in rodents, depending on the memory types examined. Te cholinergic system of the brain is a critical regulator of attention, memory, and higher-order cognitive processing, and its defcits are central to the etiology of dementia1. As such, nicotinic acetylcholine receptors (nAChRs) have gained much interest as a target of drug development 2. Neuronal nAChRs are pentameric pro- teins composed of various combinations of α (α2–α9) and β (β2–β4) nAChR subunits, diferentially expressed throughout the nervous system. -
Federal Register/Vol. 82, No. 13/Monday, January 23, 2017/Proposed Rules
8004 Federal Register / Vol. 82, No. 13 / Monday, January 23, 2017 / Proposed Rules DEPARTMENT OF HEALTH AND comment will be made public, you are www.regulations.gov. Submit both HUMAN SERVICES solely responsible for ensuring that your copies to the Division of Dockets comment does not include any Management. If you do not wish your Food and Drug Administration confidential information that you or a name and contact information to be third party may not wish to be posted, made publicly available, you can 21 CFR Part 1132 such as medical information, your or provide this information on the cover [Docket No. FDA–2016–N–2527] anyone else’s Social Security number, or sheet and not in the body of your confidential business information, such comments and you must identify this Tobacco Product Standard for N- as a manufacturing process. Please note information as ‘‘confidential.’’ Any Nitrosonornicotine Level in Finished that if you include your name, contact information marked as ‘‘confidential’’ Smokeless Tobacco Products information, or other information that will not be disclosed except in identifies you in the body of your accordance with 21 CFR 10.20 and other AGENCY: Food and Drug Administration, comments, that information will be applicable disclosure law. For more HHS. posted on http://www.regulations.gov. information about FDA’s posting of • ACTION: Proposed rule. If you want to submit a comment comments to public dockets, see 80 FR with confidential information that you 56469, September 18, 2015, or access SUMMARY: The Food and Drug do not wish to be made available to the the information at: http://www.fda.gov/ Administration (FDA) is proposing a public, submit the comment as a regulatoryinformation/dockets/ tobacco product standard that would written/paper submission and in the default.htm. -
Evaluating the Real-World Effectiveness of Bupropion Versus Varenicline for Smoking Cessation: Exploring the Role of Nicotine Metabolism and Medication Adherence
Evaluating the Real-World Effectiveness of Bupropion Versus Varenicline for Smoking Cessation: Exploring the Role of Nicotine Metabolism and Medication Adherence By Jiahui Zhang A thesis submitted in conformity with the requirements for the degree of Master of Science Graduate Department of Pharmacology and Toxicology University of Toronto © Copyright by Jiahui Zhang (2017) Evaluating the Real-World Effectiveness of Bupropion Versus Varenicline for Smoking Cessation: Exploring the Role of Nicotine Metabolism and Medication Adherence Jiahui Zhang Degree of Master of Science Graduate Department of Pharmacology and Toxicology University of Toronto ABSTRACT Bupropion and varenicline are effective, first-line prescription-only pharmacotherapies for smoking cessation; however, their real-world use is limited by affordability and accessibility. Using a novel internet-based randomized design, we evaluated the real-world effectiveness of mailed bupropion and varenicline, as well as the roles of nicotine metabolism (NMR) and medication adherence, in a sample of interested smokers using web-based recruitment and follow up. Quit rates at end of treatment (EOT) were significantly higher for varenicline (30.2%) compared to bupropion (19.6%). Quit rates at 6 months (14.0%) and 12 months (12.1%) were not significantly different between bupropion and varenicline. Increased medication compliance significantly improved cessation outcomes at EOT. NMR was associated with nicotine dependence. Varenicline benefited Slow Metabolizers of nicotine whilst bupropion benefited Normal Metabolizers. Even though real-world quit rates were comparable to clinical trials, improving medication compliance and implementing personalized pharmacological and behavioral interventions are promising approaches to increase efficacy of smoking cessation pharmacotherapies. ii ACKNOWLEDGEMENTS First and foremost, I would like to express my sincerest appreciation to my supervisor, Dr. -
(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. -
July 16, 2018 VIA ELECTRONIC SUBMISSION and HAND DELIVERY Division of Dockets Management Food and Drug Administration 5630 Fishe
Jose Luis Murillo Vice President Regulatory Affairs July 16, 2018 VIA ELECTRONIC SUBMISSION AND HAND DELIVERY Division of Dockets Management Food and Drug Administration 5630 Fishers Lane, Rm. 1061 Rockville, MD 20852 Re: Docket No. FDA-2017-N-6189 (83 Fed. Reg. 11,818, March 16, 2018) Advance Notice of Proposed Rulemaking on Tobacco Product Standard for Nicotine Level of Certain Tobacco Products Altria Client Services (“ALCS”), on behalf of Philip Morris USA Inc. (“PM USA”), John Middleton Company (“JMC”), and Sherman Group Holdings LLC and its subsidiaries (“Nat Sherman”),1 submits these comments to the Food and Drug Administration’s (“FDA’s” or the “Agency’s”) Advance Notice of Proposed Rulemaking (“ANPRM”) on a Tobacco Product Standard for Nicotine Level of Certain Tobacco Products. The ANPRM comes within the context of an industry in the midst of transformative change. Cigarette smoking is at historically low levels and continues to decline. At the same time, a new market is emerging in innovative noncombustible tobacco products that are potentially less harmful than cigarettes. There is now a scientific consensus that noncombustible products, like e-vapor, are substantially less risky than conventional cigarettes. It is smoke, and not nicotine, that causes most tobacco- related harm. And adult smokers are increasingly expressing interest in switching from cigarettes to less risky alternatives. We agree that a nicotine product standard of some sort may make sense in a future regulatory system, but this requires the pre-existence of a marketplace with alternative, FDA-authorized, reduced risk products; more information about the relative risks of those products; and a regulatory system that respects the rights of adults to make decisions based on accurate information. -
INSTITUTO DE QUÍMICA – CAMPUS ARARAQUARA Victor De Sousa Batist
UNIVERSIDADE ESTADUAL PAULISTA “JÚLIO DE MESQUITA FILHO” INSTITUTO DE QUÍMICA – CAMPUS ARARAQUARA Victor de Sousa Batista Estudos de modelagem molecular de compostos bioativos frente ao receptor nicotínico de acetilcolina do subtipo α4β2 Araraquara 2016 Victor de Sousa Batista Estudos de modelagem molecular de compostos bioativos frente ao receptor nicotínico de acetilcolina do subtipo α4β2 Trabalho de Conclusão de Curso apresentado ao Instituto de Química da Universidade Estadual Paulista “Júlio de Mesquita Filho” como parte dos requisitos para a obtenção do título de Bacharel em Química. Orientador: Prof. Dr. Nailton Monteiro do Nascimento Júnior Araraquara 2016 Victor de Sousa Batista Estudos de modelagem molecular de compostos bioativos frente ao receptor nicotínico de acetilcolina do subtipo α4β2 Trabalho de Conclusão de Curso apresentado ao Instituto de Química da Universidade Estadual Paulista “Júlio de Mesquita Filho” como parte dos requisitos para a obtenção do título de Bacharel em Química. Aprovado em _____ de ________________________ de 2016. BANCA EXAMINADORA __________________________________________ Prof. Dr. Nailton Monteiro do Nascimento Júnior Unesp – Araraquara __________________________________________ Prof. Dr. Gustavo Troiano Feliciano Unesp – Araraquara __________________________________________ Profa. Dra. Cíntia Duarte de Freitas Milagre Unesp – Araraquara Araraquara 2016 AGRADECIMENTOS Ao meu orientador, Prof. Dr. Nailton Monteiro do Nascimento Júnior, por sempre me incentivar a ultrapassar meus limites e pela -
WO 2016/001643 Al 7 January 2016 (07.01.2016) 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 2016/001643 Al 7 January 2016 (07.01.2016) P O P C T (51) International Patent Classification: (74) Agents: GILL JENNINGS & EVERY LLP et al; The A61P 25/28 (2006.01) A61K 31/194 (2006.01) Broadgate Tower, 20 Primrose Street, London EC2A 2ES A61P 25/16 (2006.01) A61K 31/205 (2006.01) (GB). A23L 1/30 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: kind of national protection available): AE, AG, AL, AM, PCT/GB20 15/05 1898 AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (22) International Filing Date: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, 29 June 2015 (29.06.2015) HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (25) Filing Language: English KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (26) Publication Language: English PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (30) Priority Data: SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 141 1570.3 30 June 2014 (30.06.2014) GB TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 1412414.3 11 July 2014 ( 11.07.2014) GB (84) Designated States (unless otherwise indicated, for every (71) Applicant: MITOCHONDRIAL SUBSTRATE INVEN¬ kind of regional protection available): ARIPO (BW, GH, TION LIMITED [GB/GB]; 39 Glasslyn Road, London GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, N8 8RJ (GB). -
Nicotinic Acetylcholine Receptor Signaling in Neuroprotection
Akinori Akaike · Shun Shimohama Yoshimi Misu Editors Nicotinic Acetylcholine Receptor Signaling in Neuroprotection Nicotinic Acetylcholine Receptor Signaling in Neuroprotection Akinori Akaike • Shun Shimohama Yoshimi Misu Editors Nicotinic Acetylcholine Receptor Signaling in Neuroprotection Editors Akinori Akaike Shun Shimohama Department of Pharmacology, Graduate Department of Neurology, School of School of Pharmaceutical Sciences Medicine Kyoto University Sapporo Medical University Kyoto, Japan Sapporo, Hokkaido, Japan Wakayama Medical University Wakayama, Japan Yoshimi Misu Graduate School of Medicine Yokohama City University Yokohama, Kanagawa, Japan ISBN 978-981-10-8487-4 ISBN 978-981-10-8488-1 (eBook) https://doi.org/10.1007/978-981-10-8488-1 Library of Congress Control Number: 2018936753 © The Editor(s) (if applicable) and The Author(s) 2018. This book is an open access publication. Open Access This book is licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made. The images or other third party material in this book are included in the book’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the book’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. The use of general descriptive names, registered names, trademarks, service marks, etc. -
Neuronal Nicotinic Receptors
NEURONAL NICOTINIC RECEPTORS Dr Christopher G V Sharples and preparations lend themselves to physiological and pharmacological investigations, and there followed a Professor Susan Wonnacott period of intense study of the properties of nAChR- mediating transmission at these sites. nAChRs at the Department of Biology and Biochemistry, muscle endplate and in sympathetic ganglia could be University of Bath, Bath BA2 7AY, UK distinguished by their respective preferences for C10 and C6 polymethylene bistrimethylammonium Susan Wonnacott is Professor of compounds, notably decamethonium and Neuroscience and Christopher Sharples is a hexamethonium,5 providing the first hint of diversity post-doctoral research officer within the among nAChRs. Department of Biology and Biochemistry at Biochemical approaches to elucidate the structure the University of Bath. Their research and function of the nAChR protein in the 1970’s were focuses on understanding the molecular and facilitated by the abundance of nicotinic synapses cellular events underlying the effects of akin to the muscle endplate, in electric organs of the acute and chronic nicotinic receptor electric ray,Torpedo , and eel, Electrophorus . High stimulation. This is with the goal of affinity snakea -toxins, principallyaa -bungarotoxin ( - Bgt), enabled the nAChR protein to be purified, and elucidating the structure, function and subsequently resolved into 4 different subunits regulation of neuronal nicotinic receptors. designateda ,bg , and d .6 An additional subunit, e , was subsequently identified in adult muscle. In the early 1980’s, these subunits were cloned and sequenced, The nicotinic acetylcholine receptor (nAChR) arguably and the era of the molecular analysis of the nAChR has the longest history of experimental study of any commenced. -
Bioactive Marine Drugs and Marine Biomaterials for Brain Diseases
Mar. Drugs 2014, 12, 2539-2589; doi:10.3390/md12052539 OPEN ACCESS marine drugs ISSN 1660–3397 www.mdpi.com/journal/marinedrugs Review Bioactive Marine Drugs and Marine Biomaterials for Brain Diseases Clara Grosso 1, Patrícia Valentão 1, Federico Ferreres 2 and Paula B. Andrade 1,* 1 REQUIMTE/Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, no. 228, 4050-313 Porto, Portugal; E-Mails: [email protected] (C.G.); [email protected] (P.V.) 2 Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS (CSIC), P.O. Box 164, Campus University Espinardo, Murcia 30100, Spain; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +351-22042-8654; Fax: +351-22609-3390. Received: 30 January 2014; in revised form: 10 April 2014 / Accepted: 16 April 2014 / Published: 2 May 2014 Abstract: Marine invertebrates produce a plethora of bioactive compounds, which serve as inspiration for marine biotechnology, particularly in drug discovery programs and biomaterials development. This review aims to summarize the potential of drugs derived from marine invertebrates in the field of neuroscience. Therefore, some examples of neuroprotective drugs and neurotoxins will be discussed. Their role in neuroscience research and development of new therapies targeting the central nervous system will be addressed, with particular focus on neuroinflammation and neurodegeneration. In addition, the neuronal growth promoted by marine drugs, as well as the recent advances in neural tissue engineering, will be highlighted. Keywords: aragonite; conotoxins; neurodegeneration; neuroinflammation; Aβ peptide; tau hyperphosphorylation; protein kinases; receptors; voltage-dependent ion channels; cyclooxygenases Mar. -
Bioorganic & Medicinal Chemistry Letters
Bioorganic & Medicinal Chemistry Letters 18 (2008) 4651–4654 Contents lists available at ScienceDirect Bioorganic & Medicinal Chemistry Letters journal homepage: www.elsevier.com/locate/bmcl Epiboxidine and novel-related analogues: A convenient synthetic approach and estimation of their affinity at neuronal nicotinic acetylcholine receptor subtypes Luca Rizzi a, Clelia Dallanoce a,*, Carlo Matera a, Pietro Magrone a, Luca Pucci b, Cecilia Gotti b, Francesco Clementi b, Marco De Amici a a Istituto di Chimica Farmaceutica e Tossicologica ‘‘Pietro Pratesi”, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy b CNR, Istituto di Neuroscienze, Farmacologia Cellulare e Molecolare e Dipartimento Farmacologia, Chemioterapia e Tossicologia Medica, Università degli Studi di Milano, Via Vanvitelli 32, 20129 Milano, Italy article info abstract Article history: Racemic exo-epiboxidine 3, endo-epiboxidine 6, and the two unsaturated epiboxidine-related derivatives Received 18 June 2008 7 and 8 were efficiently prepared taking advantage of a palladium-catalyzed Stille coupling as the key Revised 3 July 2008 step in the reaction sequence. The target compounds were assayed for their binding affinity at neuronal Accepted 4 July 2008 a4b2 and a7 nicotinic acetylcholine receptors. Epiboxidine 3 behaved as a high affinity a4b2 ligand Available online 10 July 2008 (Ki = 0.4 nM) and, interestingly, evidenced a relevant affinity also for the a7 subtype (Ki = 6 nM). Deriva- tive 7, the closest analogue of 3 in this group, bound with lower affinity at both receptor subtypes Keywords: (K = 50 nM for a4b2 and K = 1.6 lM for a7) evidenced a gain in the a4b2 versus a7 selectivity when Neuronal nicotinic acetylcholine receptors i i compared with the model compound.