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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. -
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. -
Upregulation of Peroxisome Proliferator-Activated Receptor-Α And
Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer Chih-Yang Wang, Ying-Jui Chao, Yi-Ling Chen, Tzu-Wen Wang, Nam Nhut Phan, Hui-Ping Hsu, Yan-Shen Shan, Ming-Derg Lai 1 Supplementary Table 1. Demographics and clinical outcomes of five patients with ampullary cancer Time of Tumor Time to Age Differentia survival/ Sex Staging size Morphology Recurrence recurrence Condition (years) tion expired (cm) (months) (months) T2N0, 51 F 211 Polypoid Unknown No -- Survived 193 stage Ib T2N0, 2.41.5 58 F Mixed Good Yes 14 Expired 17 stage Ib 0.6 T3N0, 4.53.5 68 M Polypoid Good No -- Survived 162 stage IIA 1.2 T3N0, 66 M 110.8 Ulcerative Good Yes 64 Expired 227 stage IIA T3N0, 60 M 21.81 Mixed Moderate Yes 5.6 Expired 16.7 stage IIA 2 Supplementary Table 2. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of an ampullary cancer microarray using the Database for Annotation, Visualization and Integrated Discovery (DAVID). This table contains only pathways with p values that ranged 0.0001~0.05. KEGG Pathway p value Genes Pentose and 1.50E-04 UGT1A6, CRYL1, UGT1A8, AKR1B1, UGT2B11, UGT2A3, glucuronate UGT2B10, UGT2B7, XYLB interconversions Drug metabolism 1.63E-04 CYP3A4, XDH, UGT1A6, CYP3A5, CES2, CYP3A7, UGT1A8, NAT2, UGT2B11, DPYD, UGT2A3, UGT2B10, UGT2B7 Maturity-onset 2.43E-04 HNF1A, HNF4A, SLC2A2, PKLR, NEUROD1, HNF4G, diabetes of the PDX1, NR5A2, NKX2-2 young Starch and sucrose 6.03E-04 GBA3, UGT1A6, G6PC, UGT1A8, ENPP3, MGAM, SI, metabolism -
Effects of the Nicotinic Agonist Varenicline, Nicotinic Antagonist R-Bpidi, and DAT Inhibitor R-Modafinil on Co-Use of Ethanol and Nicotine in Female P Rats
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Psychopharmacology Manuscript Author (Berl) Manuscript Author . Author manuscript; available in PMC 2019 May 01. Published in final edited form as: Psychopharmacology (Berl). 2018 May ; 235(5): 1439–1453. doi:10.1007/s00213-018-4853-4. Effects of the nicotinic agonist varenicline, nicotinic antagonist r-bPiDI, and DAT inhibitor R-modafinil on co-use of ethanol and nicotine in female P rats. Sarah E. Maggio1, Meredith A. Saunders1, Thomas A. Baxter1, Kimberly Nixon2, Mark A. Prendergast1, Guangrong Zheng3, Peter Crooks3, Linda P. Dwoskin2, Rachel D. Slack4, Amy H. Newman4, Richard L. Bell5, and Michael T. Bardo1 1Department of Psychology, University of Kentucky, Lexington, KY 40536, USA. 2Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA. 3Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas, Little Rock, AR 72205, USA. 4Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse- Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA. 5Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Abstract Rationale: Co-users of alcohol and nicotine are the largest group of polysubstance users worldwide. Commonalities in mechanisms of action for ethanol (EtOH) and nicotine proposes the possibility of developing a single pharmacotherapeutic to treat co-use. Objectives: Toward developing a preclinical model of co-use, female alcohol-preferring (P) rats were trained for voluntary EtOH drinking and i.v. nicotine self-administration in three phases: (1) EtOH alone (0 vs. 15%, 2-bottle choice); (2) nicotine alone (0.03 mg/kg/infusion, active vs. -
(12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 De Juan Et Al
US 200601 10428A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 de Juan et al. (43) Pub. Date: May 25, 2006 (54) METHODS AND DEVICES FOR THE Publication Classification TREATMENT OF OCULAR CONDITIONS (51) Int. Cl. (76) Inventors: Eugene de Juan, LaCanada, CA (US); A6F 2/00 (2006.01) Signe E. Varner, Los Angeles, CA (52) U.S. Cl. .............................................................. 424/427 (US); Laurie R. Lawin, New Brighton, MN (US) (57) ABSTRACT Correspondence Address: Featured is a method for instilling one or more bioactive SCOTT PRIBNOW agents into ocular tissue within an eye of a patient for the Kagan Binder, PLLC treatment of an ocular condition, the method comprising Suite 200 concurrently using at least two of the following bioactive 221 Main Street North agent delivery methods (A)-(C): Stillwater, MN 55082 (US) (A) implanting a Sustained release delivery device com (21) Appl. No.: 11/175,850 prising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more (22) Filed: Jul. 5, 2005 bioactive agents into the vitreous humor of the eye; (B) instilling (e.g., injecting or implanting) one or more Related U.S. Application Data bioactive agents Subretinally; and (60) Provisional application No. 60/585,236, filed on Jul. (C) instilling (e.g., injecting or delivering by ocular ion 2, 2004. Provisional application No. 60/669,701, filed tophoresis) one or more bioactive agents into the Vit on Apr. 8, 2005. reous humor of the eye. Patent Application Publication May 25, 2006 Sheet 1 of 22 US 2006/0110428A1 R 2 2 C.6 Fig. -
Lubeluzole/Mecamylamine Hydrochloride 1331 Precautions Ing Treated
Lubeluzole/Mecamylamine Hydrochloride 1331 Precautions ing treated. Mannitol infusion has also been used to de Manzanas; Pol.: Purisole SM; Port.: Purisole; Xarope de Macas Reinetas; Rus.: Rheogluman (Реоглюман); Spain: Salcemetic†; Salmagne; Switz.: Mannitol is contra-indicated in patients with pulmo- prevent acute renal failure during cardiovascular and Cital†. nary congestion or pulmonary oedema, intracranial other types of surgery, or after trauma. bleeding (except during craniotomy), heart failure (in To reduce raised intracranial or intra-ocular pres- patients with diminished cardiac reserve, expansion of sure mannitol may be given by intravenous infusion as Mebutamate (BAN, USAN, rINN) the extracellular fluid may lead to fulminating heart a 15 to 25% solution in a dose of 0.25 to 2 g/kg over 30 Mébutamate; Mebutamato; Mebutamatum; W-583. 2-sec-Butyl- failure), and in patients with renal failure unless a test to 60 minutes. Rebound increases in intracranial or 2-methyltrimethylene dicarbamate. dose has produced a diuretic response (if urine flow is intra-ocular pressure may occur but are less frequent Мебутамат inadequate, expansion of the extracellular fluid may than with urea. C10H20N2O4 = 232.3. lead to acute water intoxication). During transurethral prostatic resection a 2.5 to 5% CAS — 64-55-1. Mannitol should not be given with whole blood. ATC — N05BC04. solution of mannitol has been used for irrigating the ATC Vet — QN05BC04. All patients given mannitol should be carefully ob- bladder. served for signs of fluid and electrolyte imbalance and Ciguatera poisoning. Ciguatera poisoning occurs throughout O O renal function should be monitored. the Caribbean and Indopacific as a result of the consumption of certain fish contaminated with ciguatoxin; it is increasingly seen Pharmacokinetics in Europe, in travellers returning from these areas, or as a result H2NO O NH2 Only small amounts of mannitol are absorbed from the of eating imported fish. -
III IIHIIII US005574052A United States Patent (19) 11 Patent Number: 5,574,052 Rose Et Al
III IIHIIII US005574052A United States Patent (19) 11 Patent Number: 5,574,052 Rose et al. 45) Date of Patent: *Nov. 12, 1996 54) AGONIST-ANTAGONIST COMBINATION TO Nicotine Self-Administration..., H. M. Hanson, et al., Ch. REDUCE THE USE OF NICOTINE AND 7 Norman A. Krasnegor, NIDA Research Monograph 23, OTHER DRUGS Jan. 1979. Influencing Cigarette Smoking ..., I. P. Stolerman, et. al., (75 Inventors: Jed E. Rose, Venice; Edward D. Psychopharmacologia (Berl.) 28–247-249 (1973). Levin, Los Angeles, both of Calif. Effects of Mecamylamine On Human Cigarette Smoking . , Nemeth-Coslett, et al., Pharmacology (1986) (73) Assignee: Robert J. Schaap, Los Angeles, Calif.; 88:420-425. a part interest Rapid Phsiologic Effects of Nicotine ..., J. Henningfield, et al., U.S. Dept. of Health and Human Services, 259-265. * Notice: The term of this patent shall not extend Could Nicotine Antagonists Be Used..., by I. P. Stolerman, beyond the expiration date of Pat. No. Br, Jr. of Addiction (1986) 81, 47-53. 5,316,759. Mecamylamine Pretreatment . , C. S. Pomerleau, et. al., Pharmacology (1987) 91:391-393. (21) Appl. No.: 235,454 Clinical Evaluation of Mecamylamine..., F. S. Tennant, Jr., et al., NIDA Research Monograph, Feb. 9 (1984). 239–246. (22 Filed: Apr. 29, 1994 Withdrawl From Nicotine Dependence ..., F. S. Tennant, Jr., et al., NIDA Research Monograph, 55 (1985). Related U.S. Application Data Double-Blind Comparison . , F. S. Tennant, Jr., UCLA, Los Angeles, California. 63) Continuation of Ser. No. 54,144, Apr. 30, 1993, which is a Involvement of Cholinergic Nicotine-like Receptors . continuation of Ser. No. 855,868, Mar. -
Treating Smoking Dependence in Depressed Alcoholics
Treating Smoking Dependence in Depressed Alcoholics Nassima Ait-Daoud, M.D.; Wendy J. Lynch, Ph.D.; J. Kim Penberthy, Ph.D.; Alison B. Breland, Ph.D.; Gabrielle R. Marzani-Nissen, M.D.; and Bankole A. Johnson, D.Sc., M.D., Ph.D. Alcoholism and nicotine dependence share many neurobiological underpinnings; the presence of one drug can cause a person to crave the other. Depressive illness can complicate comorbid alcohol and nicotine dependence by exacerbating the negative affect encountered during attempts to abstain from one or both drugs. Given the morbidity and mortality associated with cigarette smoking, it is imperative to identify treatments to promote smoking cessation and address comorbid psychiatric conditions contemporaneously. Pharmacotherapeutic options demonstrating varying degrees of efficacy and promise in preclinical and clinical studies include nicotine replacement therapy (NRT), selective serotonin reuptake inhibitors (SSRIs), bupropion, varenicline, tricyclic antidepressants, and bupropion plus NRT. Topiramate has shown potential for promoting smoking cessation in alcoholics, although its safety in depressed patients has not been fully explored. The efficacy of medications for treating nicotine dependence is generally enhanced by the inclusion of behavioral interventions such as cognitive behavioral therapy. When group cohesion and social support are stressed, success rates increase among depressed smokers undergoing smoking cessation treatment. Additional treatment strategies targeting dually dependent individuals with -
MECAMYLAMINE Hydrochloride Tablets, USP, 2.5 Mg
MECAMYLAMINE HYDROCHLORIDE- mecamylamine hydrochloride tablet Nexgen Pharma, Inc. ---------- MECAMYLAMINE Hydrochloride Tablets, USP, 2.5 mg DESCRIPTION Mecamylamine HCl is a potent, oral antihypertension agent and ganglion blocker, and is a secondary amine. It is N,2,3,3-tetramethyl-bicyclo [2.2.1] heptan- 2 -amine hydrochloride. Its empirical formula is C11H21N • HCl and its structural formula is: It is a white, odorless, or practically odorless, crystalline powder, is highly stable, soluble in water and has a molecular weight of 203.75. Mecamylamine HCl is supplied as tablets for oral use, each containing 2.5 mg mecamylamine HCl. Inactive ingredients are calcium phosphate, D&C Yellow 10, FD&C Yellow 6, lactose, magnesium stearate, cornstarch, and talc. CLINICAL PHARMACOLOGY Mecamylamine HCl reduces blood pressure in both normotensive and hypertensive individuals. It has a gradual onset of action (1/2 to 2 hours) and a long-lasting effect (usually 6 to 12 hours or more). A small oral dosage often produces a smooth and predictable reduction of blood pressure. Although this antihypertensive effect is predominantly orthostatic, the supine blood pressure is also significantly reduced. Pharmacokinetics and Metabolism Mecamylamine HCl is almost completely absorbed from the gastrointestinal tract, resulting in consistent lowering of blood pressure in most patients with hypertensive cardiovascular disease. Mecamylamine HCl is excreted slowly in the urine in the unchanged form. The rate of its renal elimination is influenced markedly by urinary pH. Alkalinization of the urine reduces, and acidification promotes, renal excretion of mecamylamine. Mecamylamine HCl crosses the blood-brain and placental barriers. INDICATIONS AND USAGE For the management of moderately severe to severe essential hypertension and in uncomplicated cases of malignant hypertension. -
Opioid and Nicotine Use, Dependence, and Recovery: Influences of Sex and Gender
Opioid and Nicotine: Influences of Sex and Gender Conference Report: Opioid and Nicotine Use, Dependence, and Recovery: Influences of Sex and Gender Authors: Bridget M. Nugent, PhD. Staff Fellow, FDA OWH Emily Ayuso, MS. ORISE Fellow, FDA OWH Rebekah Zinn, PhD. Health Program Coordinator, FDA OWH Erin South, PharmD. Pharmacist, FDA OWH Cora Lee Wetherington, PhD. Women & Sex/Gender Differences Research Coordinator, NIH NIDA Sherry McKee, PhD. Professor, Psychiatry; Director, Yale Behavioral Pharmacology Laboratory Jill Becker, PhD. Biopsychology Area Chair, Patricia Y. Gurin Collegiate Professor of Psychology and Research Professor, Molecular and Behavioral Neuroscience Institute, University of Michigan Hendrée E. Jones, Professor, Department of Obstetrics and Gynecology; Executive Director, Horizons, University of North Carolina at Chapel Hill Marjorie Jenkins, MD, MEdHP, FACP. Director, Medical Initiatives and Scientific Engagement, FDA OWH Acknowledgements: We would like to acknowledge and extend our gratitude to the meeting’s speakers and panel moderators: Mitra Ahadpour, Kelly Barth, Jill Becker, Kathleen Brady, Tony Campbell, Marilyn Carroll, Janine Clayton, Wilson Compton, Terri Cornelison, Teresa Franklin, Maciej Goniewcz, Shelly Greenfield, Gioia Guerrieri, Scott Gottlieb, Marsha Henderson, RADM Denise Hinton, Marjorie Jenkins, Hendrée Jones, Brian King, George Koob, Christine Lee, Sherry McKee, Tamra Meyer, Jeffery Mogil, Ann Murphy, Christine Nguyen, Cheryl Oncken, Kenneth Perkins, Yvonne Prutzman, Mehmet Sofuoglu, Jack Stein, Michelle Tarver, Martin Teicher, Mishka Terplan, RADM Sylvia Trent-Adams, Rita Valentino, Brenna VanFrank, Nora Volkow, Cora Lee Wetherington, Scott Winiecki, Mitch Zeller. We would also like to thank those who helped us plan this program. Our Executive Steering Committee included Ami Bahde, Carolyn Dresler, Celia Winchell, Cora Lee Wetherington, Jessica Tytel, Marjorie Jenkins, Pamela Scott, Rita Valentino, Tamra Meyer, and Terri Cornelison. -
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. -
Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine
Neuropsychopharmacology (2015) 40, 2327–2336 © 2015 American College of Neuropsychopharmacology. All rights reserved 0893-133X/15 www.neuropsychopharmacology.org Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine 1,2 3 ,1,2,4 Erika Perez , Natalia Quijano-Cardé and Mariella De Biasi* 1 2 Department of Neuroscience, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of 3 4 Neuroscience, Baylor College of Medicine, Houston, TX, USA; University of Puerto Rico at Mayagüez, Mayagüez, Puerto Rico; Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA Alcohol and nicotine are among the top causes of preventable death in the United States. Unfortunately, people who are dependent on alcohol are more likely to smoke than individuals in the general population. Similarly, smokers are more likely to abuse alcohol. Alcohol and nicotine codependence affects health in many ways and leads to poorer treatment outcomes in subjects who want to quit. This study examined the interaction of alcohol and nicotine during withdrawal and compared abstinence symptoms during withdrawal from one of the two drugs only vs both. Our results indicate that simultaneous withdrawal from alcohol and nicotine produces physical symptoms that are more severe and last longer than those experienced during withdrawal from one of the two drugs alone. In animals experiencing withdrawal after chronic ethanol treatment, acute nicotine exposure was sufficient to prevent abstinence symptoms. Similarly, symptoms were prevented when alcohol was injected acutely in mice undergoing nicotine withdrawal. These experiments provide evidence for the involvement of the nicotinic cholinergic system in alcohol withdrawal.