DOCSLIB.ORG

Effects of Alprazolam on Driving Ability, Memory Functioning and Psychomotor Performance: a Randomized, Placebo-Controlled Study Joris C

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Effects of Alprazolam on Driving Ability, Memory Functioning and Psychomotor Performance: a Randomized, Placebo-Controlled Study Joris C Effects of Alprazolam on Driving Ability, Memory Functioning and Psychomotor Performance: A Randomized, Placebo-controlled Study Joris C. Verster, M.S., Edmund R. Volkerts, Ph.D., and Marinus N. Verbaten, Ph.D. Alprazolam is prescribed for the treatment of anxiety and performed 2.5 h after treatment administration, comprising panic disorder. Most users are presumably involved in daily the Sternberg Memory Scanning Test, a Continuous activities such as driving. However, the effects of Tracking Test, and a Divided Attention Test. Relative to alprazolam on driving ability have never been investigated. placebo, alprazolam caused serious driving impairment, as ϭ This study was conducted to determine the effects of expressed by a significantly increased SDLP (F1,19 97.3, Ͻ ϭ Ͻ alprazolam (1 mg) on driving ability, memory and p .0001) and SDS (F1,19 30.4, p .0001). This was psychomotor performance. Twenty healthy volunteers confirmed by subjective assessments showing significantly ϭ Ͻ participated in a randomized, double-blind, placebo- impaired driving quality (F1,19 16.4, p .001), decreased ϭ Ͻ controlled crossover study. One hour after oral alertness (F1,19 43.4, p .0001), decreased mental ϭ Ͻ administration, subjects performed a standardized driving activation (F1,19 5.7, p .03) and increased mental effort ϭ Ͻ test on a primary highway during normal traffic. They were during driving (F1,19 26.4, p .0001). Furthermore, instructed to drive with a constant speed (90 km/h) while alprazolam significantly impaired performance on the maintaining a steady lateral position within the right traffic laboratory tests. In conclusion, alprazolam users must be lane. Primary performance measures were the Standard warned not to drive an automobile or operate potentially Deviation of Lateral Position (SDLP) and the Standard dangerous machinery. Deviation of Speed (SDS). After the driving test, subjective [Neuropsychopharmacology 27:260–269, 2002] driving quality, mental effort, and mental activation during © 2002 American College of Neuropsychopharmacology. driving were assessed. A laboratory test battery was Published by Elsevier Science Inc. KEY WORDS: Alprazolam; Driving; Memory; Psychomotor; Alprazolam is the most frequently used drug of the Performance benzodiazepine family and is one of the 10 most pre- scribed drugs in the USA (RxList 2000). Alprazolam, a From the Utrecht Institute for Pharmaceutical Sciences, Depart- 1,4-triazolobenzodiazepine analog, has a relatively ment of Psychopharmacology, University of Utrecht, The Nether- lands. short half-life, is free from active metabolites and is Address correspondence to: Joris C. Verster, University of Utrecht, usually prescribed for the treatment of generalized anx- Utrecht Institute for Pharmaceutical Sciences, Department of Psy- iety and panic disorder. Clinical dosages of alprazolam, chopharmacology, P.O. Box 80082, 3508 TB Utrecht, The Nether- lands. Tel.: ϩ31 30 253 69 09; Fax: ϩ31 30 253 73 87; E-mail: administrated in divided doses, range from 0.5 mg to 4 [email protected] mg/day for the treatment of anxiety disorder and from Received October 1, 2001; revised February 5, 2002; accepted Feb- 6 to 10 mg/day for the treatment of panic disorder. ruary 11, 2002. Online publication: 2/14/02 at www.acnp.org/citations/ Alprazolam has also anticonvulsant and antidepres- Npp021402246. sant properties (Jonas and Cohon 1993; Petty et al. 1995; NEUROPSYCHOPHARMACOLOGY 2002–VOL. 27, NO. 2 © 2002 American College of Neuropsychopharmacology Published by Elsevier Science Inc. 0893-133X/02/$–see front matter 655 Avenue of the Americas, New York, NY 10010 PII S0893-133X(02)00310-X NEUROPSYCHOPHARMACOLOGY 2002–VOL. 27, NO. 2 Alprazolam and Driving Ability 261 Casacalenda and Boulenger 1998). Since anxiety is often short half life (Ͻ24 h), such as alprazolam (mean half accompanied by depression it is suggested that alpra- life is approximately 11 h). Some epidemiological zolam is a more powerful anxiolytic in comparison to studies, however, did specifically investigate alpra- other benzodiazepines that lack these antidepressant zolam’s effects, and an association between alpra- properties (Petty et al. 1995). The drug has a fast onset zolam use and increased risk of falling down has been to anxiety relief (less than one week) when compared shown (Mendelson 1996). with anxiety treatment with buspirone or SSRIs (two to The popularity and clinical efficacy of alprazolam four weeks). has resulted in a large number of studies concerning Besides the benefits of alprazolam’s therapeutic ef- its effects on various aspects of human performance fects, commonly reported adverse central nervous sys- and memory functioning. These studies consistently tem (CNS) effects are sedation, reduced alertness, reported significant performance impairment after drowsiness, confusion, sleepiness, dizziness and head- acute dosages (1.0 mg and higher) of alprazolam in ache. These adverse effects seem to diminish during tests measuring skills related to driving, such as track- treatment; however, they do not disappear completely ing (Ellinwood et al. 1985, 1987; Linnoila et al. 1990; (O’Sullivan et al. 1994). In addition, long-term alpra- Nikaido et al. 1990; Ellinwood et al. 1993; Vermeeren zolam treatment raised concerns about abuse potential, et al. 1995; Kroboth et al. 1998), vigilance performance drug dependency, and withdrawal phenomena. (Kožená et al. 1995; Suzuki et al. 1995) and reaction The effects of alprazolam can be explained by its speed (Hindmarch 1983; Block and Berchou 1984; Lin- pharmacological actions in the brain, where it binds noila et al. 1990; Bond et al. 1991; Danjou et al. 1992; with high affinity to the GABAA benzodiazepine recep- Saletu et al. 1994; Kroboth et al. 1998). There is, how- tor complex. Alprazolam facilitates the binding of ever, a lively debate concerning the predictive validity GABA resulting in an increased influx of chloride ions. of laboratory tests to actual on-the-road driving per- In turn, the presence of GABA inhibits the action of formance. In this context, it has been shown that labo- connected brain structures by interacting with several ratory simulation tests are not sensitive when com- other neurotransmitter systems, including noradrener- pared with actual on-the-road driving tests during gic, serotonergic, cholinergic and opioidergic systems normal traffic (Volkerts et al. 1992). (Julien 1998). The GABAA benzodiazepine receptor The effects of alprazolam on driving during normal complex comprises several subunits, of which ␣ and ␥ traffic have not yet been investigated. Referring to the subunits are able to bind benzodiazepines. Recent evi- CNS effects of alprazolam and taking its wide use into dence (Rudolph et al. 2001; Weinberger 2001) has account, the purpose of the present study was to deter- shown that these subunits can be further divided into mine the acute effects of alprazolam (1 mg) on driving ␣ ␣ ␥ ␥ numerically labeled isoforms ( 1- 6, 1- 3). It has been ability during normal traffic. In addition, driving-related ␣ shown that activation of 1 subunits mediates sedation, skills were investigated under controlled laboratory con- anterograde amnesia, and hypnotic effects of benzodi- ditions. During driving, motor control is essential to ␣ azepines, whereas activation of 2 subunits causes anti- manage safe driving. For example, the driver has to keep ␣ anxiety effects. It is therefore not surprising that 2 the car in a steady position within the traffic lane. To ex- subunits are abundantly present in the amygdala, hip- amine motor control, a tracking test was included, com- pocampus and cerebral cortex: brain structures that are prising an easy and a hard version. Also, continuous de- involved in mediating anxiety processes. mands on working memory are necessary to interact Unfortunately, the effects of alprazolam are not safely with the traffic environment. For example, the ␣ limited to ‘therapeutic meaningful’ sites of action ( 2 driver has to be aware of the approaching vehicles in the effects), since alprazolam enhances the inhibitory ef- adjacent traffic lane in order to take decisions for per- fects of GABA which causes a general slowing of brain forming overtaking maneuvers and to respond to road activity, resulting in sedation and reduced alertness signaling. Therefore, the Sternberg memory scanning ␣ ( 1 effects). test was included in the laboratory test battery. Finally, a Taking into account the large number of alprazolam divided attention test was included, since the driver has prescriptions, its ambulatory use, and adverse CNS ef- to attend to a number of traffic circumstances during fects, it is evident that the effects of alprazolam on driving that occur simultaneously. daily activities such as driving a car are of major con- cern to society. In this context, epidemiological evi- dence showed increased risk of hip fractures (Ray et HYPOTHESES al. 1987, 1989) and traffic accidents (Neutel 1995; Hem- melgarn et al. 1997; Barbone et al. 1998) after anxi- It is hypothesized that alprazolam will impair driving olytic benzodiazepine use. However, these effects ability, resulting in significantly increased SDLP and were significant only for benzodiazepines with a long SDS. It is also hypothesized that alprazolam will signif- elimination half life (Ͼ24 h), and not for those with a icantly impair laboratory test performance. 262 J.C. Verster et al. NEUROPSYCHOPHARMACOLOGY 2002–VOL. 27, NO. 2 METHODS For safety reasons, a licensed driving instructor pro-
Load more

Recommended publications
  • Drug Class Review Newer Drugs for Insomnia
    Drug Class Review Newer Drugs for Insomnia Final Update 2 Report October 2008 The Agency for Healthcare Research and Quality has not yet seen or approved this report. The purpose of Drug Effectiveness Review Project reports is to make available information regarding the comparative clinical effectiveness and harms of different drugs. Reports are not usage guidelines, nor should they be read as an endorsement of or recommendation for any particular drug, use, or approach. Oregon Health & Science University does not recommend or endorse any guideline or recommendation developed by users of these reports. Update 1: July 2006 Original: December 2005 Susan Carson, MPH Marian S. McDonagh, PharmD Sujata Thakurta, MPA:HA Po-Yin Yen, MS Drug Effectiveness Review Project Marian McDonagh, PharmD, Principal Investigator Oregon Evidence-based Practice Center Mark Helfand, MD, MPH, Director Copyright © 2008 by Oregon Health & Science University Portland, Oregon 97239. All rights reserved. Final Report Update 2 Drug Effectiveness Review Project The medical literature relating to the topic is scanned periodically (see http://www.ohsu.edu/xd/research/centers-institutes/evidence-based-policy- center/derp/documents/methods.cfm for scanning process description). Upon review of the last scan, the Drug Effectiveness Review Project governance group elected not to proceed with another full update of this report based on the information contained in the scan. Some portions of the report may not be up to date. Prior versions of this report can be accessed at the DERP website. Insomnia Page 2 of 87 Final Report Update 2 Drug Effectiveness Review Project TABLE OF CONTENTS INTRODUCTION ............................................................................................................. 6 Scope and Key Questions ......................................................................................................................
    [Show full text]
  • CNS Drug Reviews Vol
    CNS Drug Reviews Vol. 10, No. 1, pp. 45–76 © 2004 Neva Press, Branford, Connecticut Clinical Pharmacology, Clinical Efficacy, and Behavioral Toxicity of Alprazolam: A Review of the Literature Joris C. Verster and Edmund R. Volkerts Utrecht Institute for Pharmaceutical Sciences, Department of Psychopharmacology, University of Utrecht, Utrecht, The Netherlands Keywords: Alprazolam — Benzodiazepines — Anxiety — Depression — Panic — Sedation. ABSTRACT Alprazolam is a benzodiazepine derivative that is currently used in the treatment of generalized anxiety, panic attacks with or without agoraphobia, and depression. Alprazo- lam has a fast onset of symptom relief (within the first week); it is unlikely to produce de- pendency or abuse. No tolerance to its therapeutic effect has been reported. At discontinu- ation of alprazolam treatment, withdrawal and rebound symptoms are common. Hence, alprazolam discontinuation must be tapered. An exhaustive review of the literature showed that alprazolam is significantly superior to placebo, and is at least equally effective in the relief of symptoms as tricyclic antide- pressants (TCAs), such as imipramine. However, although alprazolam and imipramine are significantly more effective than placebo in the treatment of panic attacks, Selective Sero- tonin Reuptake Inhibitors (SSRIs) appear to be superior to either of the two drugs. Therefore, alprazolam is recommended as a second line treatment option, when SSRIs are not effective or well tolerated. In addition to its therapeutic effects, alprazolam produces adverse effects, such as drowsiness and sedation. Since alprazolam is widely used, many clinical studies investi- gated its cognitive and psychomotor effects. It is evident from these studies that alprazo- lam may impair performance in a variety of skills in healthy volunteers as well as in pa- tients.
    [Show full text]
  • In the Treatment of Generalised Anxiety Disorder Does Pharmacology
    Characteristics Table for The Clinical Question: In the treatment of generalised anxiety disorder does 6/18/2010 12:21:10 pharmacology improve outcome? Comparisons Included in this Clinical Question Anticonvulsants versus Placebo Anticonvulsants vs Venlafaxine (SNRI) Antihistamine vs Placebo Benzodiazepines versus vs Placebo Anticonvulsants FELTNER2003 DARCIS1995 KASPER2009 KASPER2009 LADER1998 FELTNER2003 MONTGOMERY2006 MONTGOMERY2006 LLORCA2002 PANDE2003 MONTGOMERY2008 PFIZER2005 PANDE2003 RICKELS2005 PFIZER2005 POHL2005 RICKELS2005 Benzodiazepines versus Azapirones Benzodiazepines versus Placebo Buspirone vs Placebo Duloxetine (SNRI) vs. placebo BOURIN1992 ANDREATINI2002 DAVIDSON1999 HARTFORD2007 ANSSEAU2001 LADER1998 KOPONEN2007 CUTLER1993A MAJERCSIK2003 NICOLINI2009 FELTNER2003 POLLACK1997 RYNN2008 FRESQUET2000 SRAMEK1996 HACKETT2003 LYDIARD1997 MCLEOD1992 MOLLER2001 PANDE2003 PFIZER2008 RICKELS2000B RICKELS2005 Duloxetine (SNRI) vs. Venlafaxine Quetiapine versus Placebo SSRI vs Venlafaxine SSRIs versus Placebo (SNRI) ASTRAZENECA2007A BOSE2008 ALLGULANDER2004 HARTFORD2007 ASTRAZENECA2007B ASTRAZENECA2007A NICOLINI2009 ASTRAZENECA2007C ASTRAZENECA2007B ASTRAZENECA2008 BALDWIN2006 BOSE2008 BRAWMAN-MINTZER2006 DAVIDSON2004 GOODMAN2005 GSK2002 GSK2005 HEWETT2001 LENZE2005 LENZE2009 PFIZER2008 POLLACK2001 RICKELS2003 SSRIs versus SSRIs TCA vs Placebo Venlafaxine (SNRI) versus Azapirones Venlafaxine (SNRI) versus placebo BALDWIN2006 MCLEOD1992 DAVIDSON1999 ALLGULANDER2001 BALL2005 BOSE2008 BIELSKI2005 DAVIDSON1999 GELENBERG2000 HACKETT2003
    [Show full text]
  • Drug Class Review on Newer Sedative Hypnotics
    Drug Class Review on Newer Sedative Hypnotics Final Report December 2005 The Agency for Healthcare Research and Quality has not yet seen or approved this report The purpose of this report is to make available information regarding the comparative effectiveness and safety profiles of different drugs within pharmaceutical classes. Reports are not usage guidelines, nor should they be read as an endorsement of, or recommendation for, any particular drug, use or approach. Oregon Health & Science University does not recommend or endorse any guideline or recommendation developed by users of these reports. Susan Carson, MPH Po-Yin Yen, MS Marian S. McDonagh, PharmD Oregon Evidence-based Practice Center Oregon Health & Science University Mark Helfand, MD, MPH, Director Copyright © 2005 by Oregon Health & Science University Portland, Oregon 97201. All rights reserved. Final Report Drug Effectiveness Review Project TABLE OF CONTENTS Introduction....................................................................................................................... 4 Scope and Key Questions ............................................................................................. 4 Methods.............................................................................................................................. 6 Literature Search........................................................................................................... 6 Study Selection ............................................................................................................
    [Show full text]
  • (Mmnm) and Auditory Evoked Field Component N100m
    Neuropsychopharmacology (2004) 29, 1723–1733 & 2004 Nature Publishing Group All rights reserved 0893-133X/04 $30.00 www.neuropsychopharmacology.org Effects of Lorazepam on the Neuromagnetic Mismatch Negativity (MMNm) and Auditory Evoked Field Component N100m Timm Rosburg*,1,2,3, Varvara Marinou1, Jens Haueisen2, Stefan Smesny1 and Heinrich Sauer1 1 2 Department of Psychiatry, Friedrich-Schiller-University Jena, Jena, Germany; Biomagnetic Center, Department of Neurology, Friedrich-Schiller- University Jena, Jena, Germany; 3Department of Epileptology, University of Bonn, Bonn, Germany The mismatch negativity (MMN) as an auditory evoked potential is thought to reflect an early, preconscious attention process. While this component has gained great importance in studies on clinical populations and in basic research on auditory information processing, the involvement of different neurotransmitters in the generation of this component is less well understood. We investigated the impact of the benzodiazepine lorazepam as a GABA agonist on the neuromagnetic MMN (MMNm) and auditory evoked field component N100m. A group of 12 healthy subjects was studied in single blind trials under the following three conditions: after the intake of 1.25 mg lorazepam, 100 mg caffeine or placebo. Neuromagnetic recordings were obtained before drug intake and three times after it. Controlled visual attention was tested additionally using a version of the Continuous Performance Test (CPT). The neuromagnetic activity was reconstructed by a single moving dipole, and the dipole moment and its latency were compared between conditions and time points of measurement. Lorazepam diminished the signal detection performance in the CPT 25 min after drug intake. The source of the field component N100m was attenuated, most significantly in the recording 105 min after lorazepam intake.
    [Show full text]
  • Validated Stability Indicating HPLC Method for Determination of Zolpidem in the Presence of Its Degradation Products
    The Open Conference Proceedings Journal, 2012, 3, 13-17 13 Open Access Validated Stability Indicating HPLC Method for Determination of Zolpidem in the Presence of Its Degradation Products Effat Souri*, Azadeh Shirvin, Nazanin Shabani Ravari, Farhad Alvandifar and Maliheh Barazandeh Tehrani Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran (14155-6451), Iran Abstract: Zolpidem is a hypnotic agent used for the treatment of insomnia. In this study a stability indicating HPLC method was developed for the determination of zolpidem in the presence of its degradation products. Stress degradation of zolpidem was performed under acidic, alkaline, oxidative, heat and photolytic conditions. Separation of zolpidem and its degradation products were performed on a Nova-Pak CN column using KH2PO4 30 mM and acetonitrile (65: 35, v/v at pH 6) as mobile phase. Acceptable linearity (r2 >0.999) and precision (CV value <1.5%) were achieved over the concen- tration range of 1-20 g/mL. Degradation of zolpidem was observed under acidic, alkaline, oxidative conditions and also exposure to UV light. The proposed method was used for assay determination of zolpidem tablets with no interfering from excipients. Keywords: Zolpidem, HPLC, Stability indicating, Degradation. INTRODUCTION guidelines to be used for determination of zolpidem in the presence of its degradation products. Zolpidem, 2- (4-methylphenyl)-N, N, 6- trimethyl- imidiazo [1, 2-a] pyridine-3- acetamide (Fig. 1), is a non- benzodiazepine hypnotic agent related to imidazopyridine MATERIALS AND METHODS class. Zolpidem is currently formulated as a hemitartrate salt Materials in tablets.
    [Show full text]
  • Zopiclone Produces Effects on Human Performance Similar to Flurazepam, Lormetazepam and Triazolam
    Br. J. clin. Pharmac. (1986), 21, 647-653 Zopiclone produces effects on human performance similar to flurazepam, lormetazepam and triazolam A. N. GRIFFITHS', D. M. JONES2 & A. RICHENS1 'Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff and 2Department of Applied Psychology, University of Wales Institute of Science and Technology, Cardiff 1 The cognitive function and psychomotor performance of 10 healthy male volunteers were measured following single oral doses of: zopiclone (7.5 mg), flurazepam (15 mg), lormetazepam (1 mg), triazolam (0.25 mg) and placebo. 2 The performance tests selected (stroop task, five choice serial reaction time, memory span, logical reasoning, mood and saccadic eye movement analysis) were thought to reflect aspects of normal daily activity. 3 The tests demonstrated a clear reduction of performance for all active treatments. No drug emerged as the most potent sedative overall, as each of the tests was affected to a different degree by each drug. 4 Drug effects were not qualitatively different between active treatments so that zopi- clone was indistinguishable from the three benzodiazepines with which it was compared. Keywords zopiclone benzodiazepines human performance saccadic eye movements Introduction Zopiclone is a cyclopyrrolone derivative which, (7.5 mg) has been shown to be effective as an although structurally unrelated to the benzodia- hypnotic (Wickstrom & Giercksky, 1980), zepines, shares their pharmacological profile. and furthermore, Lader & Denney (1983) Binding studies have shown that zopiclone binds reported this dose to be the preferred hypnotic to brain benzodiazepine receptors but is not dose. recognised by peripheral (renal) benzodiazepine The marketed benzodiazepines selected for receptors.
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • Quantitation of Zolpidem in Biological Fluids by Electro-Driven Microextraction Combined with Hplc-Uv Analysis
    EXCLI Journal 2018;17:349-361 – ISSN 1611-2156 Received: February 16, 2018, accepted: March 22, 2018, published: April 23, 2018 Original article: QUANTITATION OF ZOLPIDEM IN BIOLOGICAL FLUIDS BY ELECTRO-DRIVEN MICROEXTRACTION COMBINED WITH HPLC-UV ANALYSIS Saeid Yaripour1,2, Ali Mohammadi1,3*, Isa Esfanjani1, Roderick B Walker4, Saeed Nojavan5 1 Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran 2 Department of Pharmaceutical and Food Control, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran 3 Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran 4 Faculty of Pharmacy, Rhodes University, Grahamstown 6140, South Africa 5 Faculty of Chemistry, Shahid Beheshti University, Tehran, Iran * Corresponding author: Ali Mohammadi (Pharm.D., Ph.D.), P.O. Box 14155-6451, Tehran 14174, Iran. Tel: +98 – 21-88358801; fax: +98 – 21 -88358801, E-mail: [email protected] http://dx.doi.org/10.17179/excli2018-1140 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). ABSTRACT In this study, for the first time, an electro-driven microextraction method named electromembrane extraction combined with a simple high performance liquid chromatography and ultraviolet detection was developed and validated for the quantitation of zolpidem in biological samples. Parameters influencing electromembrane extrac- tion were evaluated and optimized. The membrane consisted of 2-ethylhexanol immobilized in the pores of a hollow fiber. As a driving force, a 150 V electric field was applied to facilitate the analyte migration from the sample matrix to an acceptor solution through a supported liquid membrane.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2005/0256029 A1 Murphy Et Al
    US 2005O256029A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0256029 A1 Murphy et al. (43) Pub. Date: Nov. 17, 2005 (54) METHODS AND COMPOSITIONS FOR Publication Classification ALLEVIATING STUTTERING (51) Int. Cl." ....................... A61K 38/17; A61K 31/573; (75) Inventors: John J. Murphy, Manhattan Beach, A61K 31/5513; A61K 31/473; CA (US); Kay Jorgenson D’Orlando, A61K 31/4745; A61K 31/515 Wayland, MA (US) (52) U.S. Cl. .............................. 514/2; 514/179; 514/270; 514/221; 514/300; 514/290 Correspondence Address: KATTEN MUCHIN ROSENMAN LLP (57) ABSTRACT 525 WEST MONROE STREET Methods of treating Stuttering include treating people with CHICAGO, IL 60661-3693 (US) gamma-aminobutyric acid (GABA) receptor modulators, including cyclopyrrolones. A Second active agent may be (73) Assignee: Indevus Pharmaceuticals, Inc., Lexing used with GABA receptor modulators. Active enantiomers, ton, MA active metabolites, and pharmaceutically acceptable Salts of gamma-aminobutyric acid receptor modulators, including (21) Appl. No.: 11/046,706 cyclopyrrolones, are acceptable components of the compo Filed: Feb. 1, 2005 Sitions. The cyclopyrrolone class of modulators includes (22) pagoclone, Suriclone, Zopiclone, 2-(7-chloro-2-naphthyri Related U.S. Application Data din-1,8-yl)-3-(5-methyl-2-oxohexyl)isoindolin-1-one, 2-(7- chloro-2-naphthyridin-18-yl)isoindolin-1-yl-4-acetami (63) Continuation of application No. 09/628,803, filed on dobutyrate, and 2-(7-chloro-1,8-naphthyridin-2yl)-3-(5- Jul. 28, 2000, now Pat. No. 6,855,721. methyl-5-hydroxy-2-oxohexyl)-1-isoindolinone. US 2005/0256029 A1 Nov. 17, 2005 METHODS AND COMPOSITIONS FOR 0006 Notably Wells, P.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • State of Knowledge of Drug-Impaired Driving
    State of Knowledge of Drug-Impaired Driving FINAL REPORT Technical Report Documentation Page 1. Report No. 2. Government Accession No. 3. Recipient's Catalog No. DOT HS 809 642 4. Title and Subtitle 5. Report Date September 2003 State of Knowledge of Drug-Impaired Driving 6. Performing Organization Code 7. Author(s) 8. Performing Organization Report No. Jones, R. K.; Shinar, D.; and Walsh, J. M. 9. Performing Organization Name and Address 10. Work Unit No. (TRAIS) Mid-America Research Institute 611 Main Street Winchester, MA 01890 11. Contract or Grant No. DTNH22-98-D-25079 12. Sponsoring Agency Name and Address 13. Type of Report and Period Covered National Highway Traffic Safety Administration Final Report Office of Research and Technology 400 7th Street, S.W. 14. Sponsoring Agency Code Washington, DC 20590 15. Supplementary Notes Amy Berning and Richard Compton were the Contracting Officer’s Technical Representatives for this project. 16. Abstract Examines the current state of knowledge of drug-impaired driving. The review covers a broad range of related research, including the detection and measurement of drugs in drivers, experimental research on the effect of drugs on the performance driving-related tasks, drug prevalence in various populations of drivers, drug-crash risk, and countermeasures for drug-impaired driving. The review covers scientific literature published since 1980. 17. Key Words 18. Distribution Statement drug-impaired drivers, experimental research, This report is available from the National Technical drug detection, drug measurement, Information Service, Springfield, Virginia 22161, epidemiologic research, drug-related traffic (703) 605-6000, and free of charge from the crashes, driving under the influence of drugs, NHTSA web site at www.nhtsa.dot.gov drug-crash countermeasures 19.
    [Show full text]