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Zolpidem Tartrate) Orally Disintegrating Tablets CIV
NDA 21-412 FDA Approved Labeling Text dated April 25, 2007 Page 1 TOVALT™ ODT (zolpidem tartrate) Orally Disintegrating Tablets CIV Rx Only LB Rev. 04/07 DESCRIPTION TOVALT™ ODT (zolpidem tartrate) Orally Disintegrating Tablets is a non- benzodiazepine hypnotic of the imidazopyridine class and is available in 5 mg and 10 mg tablet strengths for oral administration. Chemically, zolpidem is N,N,6-trimethyl-2-p-tolyl-imidazo[1,2-a]pyridine-3-acetamide L-( + )-tartrate (2:1). It has the following structure: Zolpidem tartrate is a white to off-white crystalline powder that is sparingly soluble in water, alcohol, and propylene glycol. It has a molecular weight of 764.88. Each TOVALT ODT includes the following inactive ingredients: Acesulfame Potassium, Glyceryl Monostearate, Hypromellose, Stearoyl Macrogolglycerides Polyacrylate Dispersion (30%), Talc, Mannitol, Microcrystalline Cellulose, Low Substituted Hydroxypropyl Cellulose, Crospovidone, Sodium Stearyl Fumarate, Silicon Dioxide, Monoammonium Glycyrrhizinate, Natural Intense Peppermint Flavour, FD&C Blue #2 (for 10mg only). CLINICAL PHARMACOLOGY Pharmacodynamics Subunit modulation of the GABAA receptor chloride channel macromolecular complex is hypothesized to be responsible for sedative, anticonvulsant, anxiolytic, and myorelaxant NDA 21-412 FDA Approved Labeling Text dated April 25, 2007 Page 2 drug properties. The major modulatory site of the GABAA receptor complex is located on its alpha (α) subunit and is referred to as the benzodiazepine (BZ) or omega (ω) receptor. At least three subtypes of the (ω) receptor have been identified. While zolpidem is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with a GABA-BZ receptor complex and shares some of the pharmacological properties of the benzodiazepines. -
Review Article New Pharmacological Therapies for Treatment of Gastroesophageal Reflux Disease
Journal of Pharmaceutical Research & Clinical Practice, Oct-Dec 2013; 3(4):11-21 Review Article New Pharmacological Therapies for Treatment of Gastroesophageal Reflux Disease *Rahul Saini1, Shanmukhananda M. P.2, Sunaina3 1. Department of Pharmacology, PGIMS, Rohtak, India. 2. Novartis, Hyderabad, India. 3. Department of Radiology, PGIMS, Rohtak, India. ABSTRACT Gastroesophageal reflux disease (GERD) is a chronic, relapsing disorder characterized by recurrent symptoms of acid reflux with esophageal injury. It rarely resolves spontaneously, and it is associated with frequent recurrences. It has adverse impact on quality of life. A variety of medications have been used in GERD treatment, and acid suppression therapy is the mainstay of treatment for GERD. Although proton pump inhibitor is the most potent acid suppressant and provides good efficacy in esophagitis healing and symptom relief, about one-third of patients with GERD still have persistent symptoms with poor response to standard dose proton pump inhibitors (PPI). These are generally well tolerated but there are associated with minor side effects such as headache, diarrhea, and abdominal pain. Newer formulations of PPI which have faster and longer duration of action and potassium-competitive acid blocker, a newer acid suppressant, are also in developing stages. Transient lower oesophageal sphincter relaxation (TLESR) is an important factor behind the occurrence of reflux, and preclinical studies have identified gamma aminobutyric acid (GABA) type B receptor (GABAB) agonists and metabotropic glutamate receptor 5 (mG1uR5) modulators as candidate drugs for modifying TLESR. Another novel therapeutic agent has focused on the underlying mechanisms of GERD, such as motility disorder, mucosal protection, and esophageal hypersensitivity are also under clinical trials. -
Proton Pump Inhibitors Act with Unprecedented Potencies
DOI: 10.1002/alz.12113 RESEARCH ARTICLE Proton pump inhibitors act with unprecedented potencies as inhibitors of the acetylcholine biosynthesizing enzyme—A plausible missing link for their association with incidence of dementia Rajnish Kumar1 Amit Kumar1 Agneta Nordberg1 Bengt Långström2 Taher Darreh-Shori1 1Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Abstract Neurobiology, Care Sciences and Society, Introduction: Several pharmacoepidemiological studies indicate that proton pump Karolinska Institutet, Stockholm, Sweden inhibitors (PPIs) significantly increase the risk of dementia. Yet, the underlying mecha- 2Department of Chemistry, Uppsala University, Uppsala, Sweden nism is not known. Here, we report the discovery of an unprecedented mode of action of PPIs that explains how PPIs may increase the risk of dementia. Correspondence TaherDarreh-Shori, Division of Clinical Geri- Methods: Advanced in silico docking analyses and detailed enzymological assess- atrics, Center for Alzheimer Research, Depart- ments were performed on PPIs against the core-cholinergic enzyme, choline- ment of Neurobiology, Care Sciences and Society, Karolinska Institutet, NEO, 7th Floor, 141 52 acetyltransferase (ChAT), responsible for biosynthesis of acetylcholine (ACh). Stockholm, Sweden. Results: This report shows compelling evidence that PPIs act as inhibitors of ChAT, with Email: [email protected] high selectivity and unprecedented potencies that lie far below their in vivo plasma and Funding information brain concentrations. the international Alzheimer Association, USA, Grant/Award Number: 2016-NIRG-391599; Discussion: Given that accumulating evidence points at cholinergic dysfunction as a Swedish Research Council, Grant/Award Num- driving force of major dementia disorders, our findings mechanistically explain how ber: project no 2016-01806 prolonged use of PPIs may increase incidence of dementia. -
4 Supplementary File
Supplemental Material for High-throughput screening discovers anti-fibrotic properties of Haloperidol by hindering myofibroblast activation Michael Rehman1, Simone Vodret1, Luca Braga2, Corrado Guarnaccia3, Fulvio Celsi4, Giulia Rossetti5, Valentina Martinelli2, Tiziana Battini1, Carlin Long2, Kristina Vukusic1, Tea Kocijan1, Chiara Collesi2,6, Nadja Ring1, Natasa Skoko3, Mauro Giacca2,6, Giannino Del Sal7,8, Marco Confalonieri6, Marcello Raspa9, Alessandro Marcello10, Michael P. Myers11, Sergio Crovella3, Paolo Carloni5, Serena Zacchigna1,6 1Cardiovascular Biology, 2Molecular Medicine, 3Biotechnology Development, 10Molecular Virology, and 11Protein Networks Laboratories, International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 34149, Trieste, Italy 4Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy 5Computational Biomedicine Section, Institute of Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany 6Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy 7National Laboratory CIB, Area Science Park Padriciano, Trieste, 34149, Italy 8Department of Life Sciences, University of Trieste, Trieste, 34127, Italy 9Consiglio Nazionale delle Ricerche (IBCN), CNR-Campus International Development (EMMA- INFRAFRONTIER-IMPC), Rome, Italy This PDF file includes: Supplementary Methods Supplementary References Supplementary Figures with legends 1 – 18 Supplementary Tables with legends 1 – 5 Supplementary Movie legends 1, 2 Supplementary Methods Cell culture Primary murine fibroblasts were isolated from skin, lung, kidney and hearts of adult CD1, C57BL/6 or aSMA-RFP/COLL-EGFP mice (1) by mechanical and enzymatic tissue digestion. Briefly, tissue was chopped in small chunks that were digested using a mixture of enzymes (Miltenyi Biotec, 130- 098-305) for 1 hour at 37°C with mechanical dissociation followed by filtration through a 70 µm cell strainer and centrifugation. -
Original Research Article
Original Research Article IN SILICO LIGAND-BASED 2D PHARMACOPHORE GENERATION FOR H+/K+ ATPASE INHIBITORS ABSTRACT Objectives: At the beginning of the 20th century, Peptic Ulcer became the most prevalent disease as Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) proved ineffective. Researches proved proton pump inhibitors as most successful drugs for the treatment of peptic ulcer. Hence, a ligand based pharmacophore was generated on LigandScout based on fifteen selected H+/K+ ATPase inhibitors. Methods: A pharmacophore model with three Hydrogen bond acceptors, one Hydrogen bond donor and one Hydrophobic Domain was developed. The distance between these features was estimated on Visual Molecular Dynamics (VMD) software. Results: The range between HBA-HBD was found to be 1.89-2.96A. The range between HBD-HP was 4.00-5.46A and range between HP-HBA was 1.89-2.96A. Conclusion: This research study will thus help in designing new and effective drugs for the treatment of peptic ulcer disease. Key words: Peptic Ulcer, NSAIDs, ligand, pharmacophore, Visual Molecular Dynamics INTRODUCTION Gastric H+/K+ ATPase pump is located in the parietal cells [1] and plays a crucial role in the formation of ulcers in the stomach. H pylori transmission occurs in 50% of the people worldwide [2]. A peptic ulcer is caused by Helicobacter pylori (H. pylori) infection in the gastric mucosal lining. This bacterium causes inflammation in the lining of the stomach. In response to this, gastrin hormone stimulates the gastric acid production. High levels of gastrin cause the enhance release of acid through H+/K+ ATPase pump and lead to the formation of the ulcer. -
Herbal Remedies and Their Possible Effect on the Gabaergic System and Sleep
nutrients Review Herbal Remedies and Their Possible Effect on the GABAergic System and Sleep Oliviero Bruni 1,* , Luigi Ferini-Strambi 2,3, Elena Giacomoni 4 and Paolo Pellegrino 4 1 Department of Developmental and Social Psychology, Sapienza University, 00185 Rome, Italy 2 Department of Neurology, Ospedale San Raffaele Turro, 20127 Milan, Italy; [email protected] 3 Sleep Disorders Center, Vita-Salute San Raffaele University, 20132 Milan, Italy 4 Department of Medical Affairs, Sanofi Consumer HealthCare, 20158 Milan, Italy; Elena.Giacomoni@sanofi.com (E.G.); Paolo.Pellegrino@sanofi.com (P.P.) * Correspondence: [email protected]; Tel.: +39-33-5607-8964; Fax: +39-06-3377-5941 Abstract: Sleep is an essential component of physical and emotional well-being, and lack, or dis- ruption, of sleep due to insomnia is a highly prevalent problem. The interest in complementary and alternative medicines for treating or preventing insomnia has increased recently. Centuries-old herbal treatments, popular for their safety and effectiveness, include valerian, passionflower, lemon balm, lavender, and Californian poppy. These herbal medicines have been shown to reduce sleep latency and increase subjective and objective measures of sleep quality. Research into their molecular components revealed that their sedative and sleep-promoting properties rely on interactions with various neurotransmitter systems in the brain. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that plays a major role in controlling different vigilance states. GABA receptors are the targets of many pharmacological treatments for insomnia, such as benzodiazepines. Here, we perform a systematic analysis of studies assessing the mechanisms of action of various herbal medicines on different subtypes of GABA receptors in the context of sleep control. -
Drug Points BMJ: First Published As 10.1136/Bmj.318.7192.1179 on 1 May 1999
Papers Drug points BMJ: first published as 10.1136/bmj.318.7192.1179 on 1 May 1999. Downloaded from Hepatotoxicity associated with zolpidem respectively. Retrograde endoscopic cholangiography had treatment shown no abnormality. David Karsenti, Pascal Blanc, Yannick Bacq, Etienne-Henry Metman, Six months later, in April 1997, she had had another Service d’Hépato-Gastroentérologie, Centre Hospitalier Universitaire episode of abdominal pain. Eleven days later alanine Trousseau, and Service de Pharmacologie Clinique, Centre aminotransferase and ã-glutamyl transpeptidase activities Hospitalier Universitaire Bretonneau, F-37044 Tours Cedex, France had been 50 IU/l and 89 IU/l respectively. Zolpidem is a hypnotic drug of the imidazopyridine In June 1997 ultrasound examination of the biliary group. Another imidazopyridine, alpidem, has been with- tract gave normal results. On questioning she remem- 12 drawn from the market because of its hepatotoxicity. bered that zolpidem had been reintroduced because her Hepatoxicity has been suspected in association with zolpi- insomnia had recurred (she had taken 20 mg two days dem, but it has not been clearly established because of before the last acute episode). Viral hepatitis and concur- 34 concomitant drug treatment. We report a case of acute rent infections with Epstein-Barr virus and cytomegalovi- hepatitis mimicking biliary lithiasis after treatment with rus were excluded. No antibodies against smooth muscle, zolpidem alone at a therapeutic dose, with reappearance liver and kidney microsomes, or liver cytosol or mitochon- of the hepatoxicity after the drug was reintroduced. dria were detected in serum. Five months later the results A 53 year old woman was admitted in June 1997 for of liver function tests remained within normal limits and investigation of recurrent abdominal pain. -
HS 172 R5/13 Briefly Review the Objectives, Content and Activities of This Session
HS 172 R5/13 Briefly review the objectives, content and activities of this session. Upon successfully completing this session the participant will be able to: • Explain a brief history of the CNS Depressant category of drugs. • Identify common drug names and terms associated with this category. • Identify common methods of administration for this category. • Describe the symptoms, observable signs and other effects associated with this category. CONTENT SEGMENTS LEARNING ACTIVITIES A. Overview of the Category Instructor-Led Presentations B. Possible Effects Instructor Led Demonstrations C. OtdDtifEfftOnset and Duration of Effects RdiAiReading Assignmen ts D. Overdose Signs and Symptoms Video Presentations E. Expected Results of the Evaluation Slide Presentations F. Classification Exemplar HS 172 R5/13 9-2 • Explain the typical time parameters, i.e. onset and duration of effects, associated with this category. • List the clues that are likely to emerge when the drug influence evaluation is conducted for a person under the influence of this category of drugs. • Correctly answer the “topics for study” questions at the end of this session. HS 172 R5/13 9-3 A. Overview of the Category CNS Depressants Central Nervous System Depressants slow down the operations of the brain. Point out that other common names for CNS Depressants are “downers” and “sedative-hypnotics.” • Depressants first affect those arareaseas of the brain that control a person’ s conscious, voluntary actions. • Judgment, inhibitions and reaction time are some of the things that CNS Depressants affect first. • As the dose is increased, depressants begin to affect the parts of the brain that control the body’s automatic processes, heartbeat, respiration, etc. -
Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG . -
(12) Patent Application Publication (10) Pub. No.: US 2012/0122919 A1 Schutze Et Al
US 2012O122919A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0122919 A1 Schutze et al. (43) Pub. Date: May 17, 2012 (54) PHARMACEUTICAL COMPOSITION (30) Foreign Application Priority Data COMBINING TENATOPRAZOLE AND A HISTAMINE H2-RECEPTOR ANTAGONST Oct. 21, 2002 (FR) ...................................... 02/13114 (75) Inventors: Francois Schutze, Saint-Nom-La-Breteche (FR); Suzy Publication Classification Charbit, Creteil (FR); Hervé (51) Int. Cl. Ficheux, Nogent-sur-Marne (FR): A63L/437 (2006.01) Michel Homerin, Courcouronnes A6IPL/04 (2006.01) (FR); Alain Taccoen, Le Chesnay (FR); Nathalie Taccoen, legal representative, La Chesnay (FR); (52) U.S. Cl. ........................................................ S14/303 Yoshio Inaba, Tokyo (JP) (73) Assignees: MTSUBISH PHARMA CORPORATION, Tokyo (JP); (57) ABSTRACT SIDEM PHARMA, Luxembourg (LU) The invention relates to a novel pharmaceutical combination. The inventive pharmaceutical composition, which is intended (21) Appl. No.: 13/297,122 for the treatment of pathologies linked to gastric hyperacidity, (22) Filed: Nov. 15, 2011 comprises a combination of tenatoprazole and one or more O O histamine H2-receptor antagonists preferably selected from Related U.S. Application Data cimetidine, ranitidine, famotidine and nizatidine. The inven (63) Continuation of application No. 10/532,114, filed on tion is particularly suitable for the treatment of duodenal and Jun. 23, 2006, now abandoned, filed as application No. gastric ulcers and the symptoms of, and lesions caused by, PCT/FR2003/003124 on Oct. 21, 2003. gastroesophageal reflux. US 2012/O 122919 A1 May 17, 2012 PHARMACEUTICAL COMPOSITION nist Such as famotidine, with at least two standard antacids COMBINING TENATOPRAZOLE ANDA Such as Sodium bicarbonate and magnesium hydroxide, HISTAMINE H2-RECEPTOR ANTAGONST which display a strong neutralisation potential, and an alu minium hydroxide gel which exhibits weak neutralisation RELATED APPLICATIONS potential. -
Pharmacological Aspects
Pharmacological aspects Psychopharmacology of anxiety disorders Giovanni B. Cassano, MD; Nicolò Baldini Rossi, MD; Stefano Pini, MD A nxiety disorders are the most common and among the most disabling of mental disorders in adults and adolescents.1 Although many are highly circum- scribed fears of mild-to-moderate severity, it has been estimated by the Epidemiological Catchment Area (ECA) study2 that approximately one quarter of people will experience severe symptoms, disability, and handicap as a consequence of anxiety disorders at some time dur- ing their lifetime.These disorders are associated with sig- nificant morbidity3 and increased mortality, probably as a consequence of increased suicide rates among suffer- Exposure of the general population to a 1:4 lifetime risk of ers.The direct and indirect costs to the health service and disabling anxiety has inspired generations of fundamental economy are considerable.Although persons who suffer and clinical psychopharmacologists, from the era of the from anxiety disorders are high consumers of all types of earliest benzodiazepines (BZ) to that of the selective sero- health services, only a minority receive specific help.4 tonin reuptake inhibitors (SSRIs) and related compounds, The spectrum of anxiety disorders includes generalized eg, the serotonin and norepinephrine reuptake inhibitors anxiety disorder (GAD), panic disorder (PD) and ago- (SNRIs). This comprehensive practical review summarizes raphobia, obsessive-compulsive disorder (OCD), phobic current therapeutic research across the spectrum of indi- disorder (including social phobia), and posttraumatic vidual disorders: generalized anxiety disorder (GAD), panic stress disorder (PTSD). With the discovery of new psy- disorder (PD) and agoraphobia (social anxiety disorder), chotropic medications, specific diagnosis within this spec- compulsive disorder (OCD), phobic disorder (including trum is essential because each of these disorders social phobia), and posttraumatic stress disorder (PTSD). -
25 Years of Proton Pump Inhibitors: a Comprehensive Review
Gut and Liver, Vol. 11, No. 1, January 2017, pp. 27-37 Review 25 Years of Proton Pump Inhibitors: A Comprehensive Review Daniel S. Strand1, Daejin Kim2, and David A. Peura1 1Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA, USA, and 2Division of Gastroenterology, Daegu Fatima Hospital, Daegu, Korea Proton pump inhibitors (PPIs) were clinically introduced more the modern gastroenterologist. For most, this class of drugs rep- than 25 years ago and have since proven to be invaluable, resents the first choice for treatment of esophagitis, nonerosive safe, and effective agents for the management of a variety of reflux disease (NERD), peptic ulcer disease (PUD), prevention of acid-related disorders. Although all members in this class act nonsteroidal anti-inflammatory drugs (NSAID) associated ulcers, in a similar fashion, inhibiting active parietal cell acid secre- Zollinger-Ellison syndrome (ZES), and functional dyspepsia.4-6 tion, there are slight differences among PPIs relating to their In combination with antibiotics, PPIs are also an integral part of pharmacokinetic properties, metabolism, and Food and Drug eradication therapy for Helicobacter pylori.7 Administration (FDA)-approved clinical indications. Neverthe- Despite an excellent safety profile throughout their first two less, each is effective in managing gastroesophageal reflux decades of use, the nearly universal popularity of PPIs has disease and uncomplicated or complicated peptic ulcer dis- prompted several concerns about both their short- and long- ease. Despite their overall efficacy, PPIs do have some limita- term effects.8,9 This review will examine the pharmacokinetics tions related to their short plasma half-lives and requirement and pharmacodynamics of these drugs and provide an update for meal-associated dosing, which can lead to breakthrough on both the clinical use of and remaining challenges with PPIs.