DOCSLIB.ORG

Investigating the Role of the Central and the Peripheral Benzodiazepine Receptor on Stress and Anxiety Related Parameters

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Investigating the Role of the Central and the Peripheral Benzodiazepine Receptor on Stress and Anxiety Related Parameters Investigating the role of the central and the peripheral benzodiazepine receptor on stress and anxiety related parameters Inaugural-Dissertation zur Erlangung der Doktorwürde der Fakultät für Humanwissenschaften der Universität Regensburg vorgelegt von LISA-MARIE BAHR aus Hausen Regensburg 2020 Erstgutachter: Prof. Dr. rer. soc. Andreas Mühlberger Zweitgutachterin: PD Dr. med. habil. Caroline Nothdurfter I ACKNOWLEDGEMENT I wish to thank a number of people that have supported me on this exciting journey and substantially contributed to the success of this work. First of all, I want to thank my supervisors Priv.-Doz. Caroline Nothdurfter and Professor Andreas Mühlberger for always promoting me, being open for any kind of questions and teaching me to take responsibilities. Likewise, I want to thank Professor Jens Schwarzbach for the patient teaching in the fields of brain imaging and for the support in the analysis of our MRI data. Furthermore, I want to thank Professor Rainer Rupprecht for the comprehensive support in organizational and economic matters. I am thankful for the great time and the opportunities I had within my graduate school and wish to thank its spokesperson Professor Inga Neumann and all other supervisors and PhD students of the program, especially Viola Wagner and Kerstin Kuffner for going through this together. The realization of the study would not have been possible without a number of people and I want to thank Franziska Maurer and Kevin Weber for their extensive help in data acquisition, Dr. Johannes Weigl and Dr. Andre Manook for their support concerning the medical parts, Professor Thomas Wetter for the study monitoring, Doris Melchner, Anett Dörfelt, Dr. Vladimir Milenkovic, Heike Hallof-Buestrich and Tatjana Jahner for the laboratory analyses and countless hours on improving the techniques, the study nurses of the research station 18 D for the strong support at physical examinations and in organizational matters, Viola Wagner, Philipp Seidel and Marlene Tahedl for the support at the MRI scanner, Andreas Ruider and Andreas Hennings for always being achievable in technical questions as well as Dr. Theresa Wechsler, Dr. Stefanie Biehl and Michael Pfaller for the input and discussions about the analyses. Furthermore, I want to thank our collaborators that accomplished some of the laboratory analyses including the team of Georg Weinfurtner at the medbo Regensburg as well as Priv.- Doz. Jörg Reinders at the IfADo Dortmund. Further thanks go to audEERING in Gilching for providing the speech analysis component. Special thanks go to my family, especially my parents, my brother and Johannes who always supported me and all my ideas and stood behind me no matter if happy or tough times. A loving Miau goes to Gustav and Renate. Further, I want to thank my friends who always lent an ear and sometimes got me out of the rat race. Finally, a great thanks goes to all the volunteers that participated in our clinical trial and thereby even made this work possible. II III ABSTRACT Anxiety disorders belong to the most prevalent mental disorders worldwide implying a high burden of illness. Due to their complexity and variety of underlying dysfunctions, it remains a challenging task to find optimum pharmacological treatment. Benzodiazepines, which modulate the GABAA or central benzodiazepine receptor, are among the most frequently used substances in this field. However, they hold several side effects, especially at longer application. In the search for alternatives, substances that target the translocator protein (TSPO), also known as peripheral benzodiazepine receptor, yield promising candidates. Within the present work, we aimed to compare the effects of a benzodiazepine and a TSPO ligand, which further binds to GABAA receptors, on stress and anxiety related parameters. Within a randomized clinical trial, 60 healthy male subjects received either a daily dose of 1.5 mg alprazolam, 150 mg etifoxine or placebo for a period of five days. We applied the Trier Social Stress Test in Virtual Reality, the NPU Threat Test, resting-state functional imaging, and the Continuous Performance Test and assessed self-reports, physiological parameters, salivary and blood markers, objective performance parameters as well as changes of functional brain connectivity. While alprazolam blunted the response of the HPA axis to acute psychosocial stress, etifoxine increased expression of TSPO independent of additional external stimulation. There were no effects of the medication on subjective or physiological measures of the stress response. Neither alprazolam nor etifoxine had an impact on the anxiety-related startle reflex, while etifoxine attenuated the fear-potentiated startle on day 1 of treatment. Alprazolam increased functional neuronal connectivity within and between several resting-state networks. In neither group, there was strong impairment of alertness or any serious adverse event or study dropout. When focusing on symptoms related to sedation, there were more reports from subjects that had received alprazolam. The present work revealed different effects of the applied substances on molecular, physiological and neuronal markers of stress and anxiety. Thereby, especially the strength with which the GABAergic system is affected seems to play an important role, while the involvement of TSPO might be rather specific and dependent on the respective pathological state. IV ZUSAMMENFASSUNG Angststörungen gehören zu den häufigsten psychischen Erkrankungen weltweit und gehen mit einer hohen Belastung einher. Auf Grund ihrer Komplexität und Vielzahl an zugrunde liegenden Dysfunktionen bleibt es eine Herausforderung, optimale pharmakologische Behandlung zu erhalten. Benzodiazepine, welche den GABAA bzw. zentralen Benzodiazepinrezeptor modulieren, gehören zu den am häufigsten eingesetzten Substanzen in diesem Bereich. Sie verursachen jedoch, vor allem bei längerer Anwendung, zahlreiche Nebenwirkungen. Auf der Suche nach Alternativen stellen Substanzen, die das Translokator Protein (TSPO), auch bekannt als peripherer Benzodiazepinrezeptor, forcieren, vielversprechende Kandidaten dar. Ziel der vorliegenden Arbeit war es, die Effekte eines Benzodiazepins und eines TSPO Liganden, der ferner an GABAA Rezeptoren bindet, auf Stress- und angstassoziierte Parameter zu vergleichen. Im Rahmen einer randomisierten klinische Studie erhielten 60 gesunde männliche Probanden entweder täglich 1.5 mg Alprazolam, 150 mg Etifoxin oder Placebo über einen Zeitraum von fünf Tagen. Wir setzten den Trier Sozialen Stress Tests in Virtueller Realität, den NPU Threat Test, funktionelle Bildgebung während Ruhe und den Continuous Performance Test ein und erfassten Selbstberichte, physiologische Parameter, Speichel- und Blutmarker, objektive Leistungsparameter sowie Veränderungen der funktionellen Konnektivität im Gehirn. Während Alprazolam die Reaktion der HPA Achse auf akuten psychosozialen Stress reduziere, erhöhte Etifoxin die Expression von TSPO unabhängig von weiterer externer Stimulation. Es zeigten sich keine Effekte der Medikation auf subjektive oder physiologische Parameter der Stressreaktion. Weder Alprazolam noch Etifoxin beeinflussten den Angst- bezogenen Schreckreflex, während Etifoxin den Furcht-potenzierten Startle an Tag 1 der Behandlung reduzierte. Alprazolam erhöhte die funktionelle neuronale Konnektivität innerhalb und zwischen verschiedenen Ruhenetzwerken. In keiner der Gruppen zeigte sich eine merkliche Beeinträchtigung der Aufmerksamkeit und es waren keine schwerwiegenden unerwünschten Ereignisse oder Studienabbrüche zu verzeichnen. Mit Fokus auf unerwünschte Ereignisse in Zusammenhang mit Sedierung gab es mehr Berichte von Probanden, die Alprazolam erhalten hatten. Die vorliegende Arbeit ergab unterschiedliche Effekte der eingesetzten Substanzen auf molekulare, physiologische und neuronale Marker von Stress und Angst. Dabei scheint vor allem die Stärke, mit der das GABAerge System beeinflusst wird, eine entscheidende Rolle zu spielen, während die Beteiligung von TSPO eher spezifisch und abhängig vom jeweiligen pathologischen Zustand zu sein scheint. V CONTENT LIST OF FIGURES .................................................................................................................. IX LIST OF TABLES ................................................................................................................... XI ABBREVIATIONS ............................................................................................................... XIII CHAPTER 1: General introduction ........................................................................................... 1 1.1 Overview ................................................................................................................... 2 1.2 Stress ......................................................................................................................... 2 1.2.1 Overview of stress concepts ................................................................................. 2 1.2.2 Major physiological stress systems ...................................................................... 4 1.2.3 Chronic stress and disease: focus on anxiety disorders ........................................ 9 1.3 Anxiolytic therapy ................................................................................................... 10 1.3.1 Overview of established anxiolytics and related target systems ........................ 11 1.3.2 Central benzodiazepine receptor: GABAA receptor ..........................................
Load more

Recommended publications
  • (12) Patent Application Publication (10) Pub. No.: US 2004/0224012 A1 Suvanprakorn Et Al
    US 2004O224012A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0224012 A1 Suvanprakorn et al. (43) Pub. Date: Nov. 11, 2004 (54) TOPICAL APPLICATION AND METHODS Related U.S. Application Data FOR ADMINISTRATION OF ACTIVE AGENTS USING LIPOSOME MACRO-BEADS (63) Continuation-in-part of application No. 10/264,205, filed on Oct. 3, 2002. (76) Inventors: Pichit Suvanprakorn, Bangkok (TH); (60) Provisional application No. 60/327,643, filed on Oct. Tanusin Ploysangam, Bangkok (TH); 5, 2001. Lerson Tanasugarn, Bangkok (TH); Suwalee Chandrkrachang, Bangkok Publication Classification (TH); Nardo Zaias, Miami Beach, FL (US) (51) Int. CI.7. A61K 9/127; A61K 9/14 (52) U.S. Cl. ............................................ 424/450; 424/489 Correspondence Address: (57) ABSTRACT Eric G. Masamori 6520 Ridgewood Drive A topical application and methods for administration of Castro Valley, CA 94.552 (US) active agents encapsulated within non-permeable macro beads to enable a wider range of delivery vehicles, to provide longer product shelf-life, to allow multiple active (21) Appl. No.: 10/864,149 agents within the composition, to allow the controlled use of the active agents, to provide protected and designable release features and to provide visual inspection for damage (22) Filed: Jun. 9, 2004 and inconsistency. US 2004/0224012 A1 Nov. 11, 2004 TOPCAL APPLICATION AND METHODS FOR 0006 Various limitations on the shelf-life and use of ADMINISTRATION OF ACTIVE AGENTS USING liposome compounds exist due to the relatively fragile LPOSOME MACRO-BEADS nature of liposomes. Major problems encountered during liposome drug Storage in vesicular Suspension are the chemi CROSS REFERENCE TO OTHER cal alterations of the lipoSome compounds, Such as phos APPLICATIONS pholipids, cholesterols, ceramides, leading to potentially toxic degradation of the products, leakage of the drug from 0001) This application claims the benefit of U.S.
    [Show full text]
  • Suggested Biomarkers for Major Depressive Disorder
    280 Arch Neuropsychiatry 2018;55:280−290 REVIEW https://doi.org/10.5152/npa.2017.19482 Suggested Biomarkers for Major Depressive Disorder Yunus HACIMUSALAR1 , Ertuğrul EŞEL2 1Department of Psychiatry, Kayseri Training and Research Hospital, Kayseri, Turkey 2Department of Psychiatry, Erciyes University Faculty of Medicine, Kayseri, Turkey ABSTRACT Currently, the diagnosis of major depressive disorder (MDD) mainly the hypothalamo-pituitary-adrenal axis, cytokines, and neuroimaging relies on clinical examination and subjective evaluation of depressive may be strong candidates for being biomarkers MDD, and may provide symptoms. There is no non-invasive, quantitative test available today critical information in understanding biological etiology of depression. for the diagnosis of MDD. In MDD, exploration of biomarkers will be Although the findings are not sufficient yet, we think that the results of helpful in diagnosing the disorder as well as in choosing a treatment, epigenetic studies will also provide very important contributions to the and predicting the treatment response. In this article, it is aimed to biomarker research in MDD. review the findings of suggested biomarkers such as growth factors, cytokines and other inflammatory markers, oxidative stress markers, The availability of biomarkers in MDD will be an advancement that will endocrine markers, energy balance hormones, genetic and epigenetic facilitate the diagnosis of the disorder, treatment choices in the early features, and neuroimaging in MDD and to evaluate how these findings stages, and prediction of the course of the disorder. contribute to the pathophysiology of MDD, the prediction of treatment response, severity of the disorder, and identification of subtypes. Among Keywords: Depression, biomarkers, brain-derived neurotrophic factor, these, the findings related to the brain-derived neurotrophic factor, cytokines, genetics, neuroimaging Cite this article as: Hacımusalar Y, Eşel E.
    [Show full text]
  • The Anxiolytic Etifoxine Protects Against Convulsant and Anxiogenic
    Alcohol 43 (2009) 197e206 The anxiolytic etifoxine protects against convulsant and anxiogenic aspects of the alcohol withdrawal syndrome in mice Marc Verleye*, Isabelle Heulard, Jean-Marie Gillardin Biocodex-De´partement de Pharmacologie-Zac de Mercie`res, Chemin d’Armancourt 60200 Compie`gne, France Received 11 December 2008; received in revised form 3 February 2009; accepted 4 February 2009 Abstract Change in the function of g-aminobutyric acidA (GABAA) receptors attributable to alterations in receptor subunit composition is one of main molecular mechanisms with those affecting the glutamatergic system which accompany prolonged alcohol (ethanol) intake. These changes explain in part the central nervous system hyperexcitability consequently to ethanol administration cessation. Hyperexcitability associated with ethanol withdrawal is expressed by physical signs, such as tremors, convulsions, and heightened anxiety in animal models as well as in humans. The present work investigated the effects of anxiolytic compound etifoxine on ethanol-withdrawal paradigms in a mouse model. The benzodiazepine diazepam was chosen as reference compound. Ethanol was given to NMRI mice by a liquid diet at 3% for 8 days, then at 4% for 7 days. Under these conditions, ethanol blood level ranged between 0.5 and 2 g/L for a daily ethanol intake varying from 24 to 30 g/kg. These parameters permitted the emergence of ethanol-withdrawal symptoms once ethanol administration was terminated. Etifoxine (12.5e25 mg/kg) and diazepam (1e4 mg/kg) injected intraperitoneally 3 h 30 min after ethanol removal, decreased the severity in handling-induced tremors and convulsions in the period of 4e6 h after withdrawal from chronic ethanol treatment.
    [Show full text]
  • Etifoxine Impairs Neither Alertness Nor Cognitive Functions of the Elderly: a Randomized, Double-Blind, Placebo-Controlled Crossover Study
    ARTICLE IN PRESS JID: NEUPSY [m6+; June 28, 2018;22:42 ] European Neuropsychopharmacology (2018) 000, 1–8 www.elsevier.com/locate/euroneuro Etifoxine impairs neither alertness nor cognitive functions of the elderly: A randomized, double-blind, placebo-controlled crossover study a ,b , ∗ c b D. Deplanque , F. Machuron , N. Waucquier , b b b a E. Jozefowicz , S. Duhem , S. Somers , O. Colin , c a A. Duhamel , R. Bordet a Univ. Lille, Inserm, CHU Lille, U1171 - Degenerative & Vascular cognitive disorders, F-59000 Lille, France b Univ. Lille, Inserm, CHU Lille, CIC 1403 - Centre d’Investigation Clinique, F-59000 Lille, France c Univ. Lille, CHU Lille, EA 2694 - Santé publique: épidémiologie et qualité des soins, F-59000 Lille, France Received 22 December 2017; received in revised form 4 May 2018; accepted 17 May 2018 Available online xxx KEYWORDS Abstract Etifoxine; Etifoxine hydrochloride (Stresam ®), a treatment indicated for psychosomatic manifestations of Benzodiazepines; anxiety, could be an alternative to benzodiazepines. While no impact on alertness and cognitive Anxiolytic; functions has been proven among youth, data on elderly are lacking. The primary objective of Cognition; this study was to measure the impact of etifoxine, lorazepam or placebo on alertness in the el- Elderly; derly. The secondary objectives were to evaluate cognitive performances and adverse effects. Geriatric psychiatry In this randomized, placebo-controlled, double-blind, 3-way crossover design, 30 healthy vol- unteers aged 65 to 75 years underwent three one-day sessions. After treatment intake, stan- dardized cognitive tests were conducted using the Cambridge Neuropsychological Test Auto- mated Batteries and other psychological tests (Stroop, Rey Auditory Verbal Learning Test, Digit R Registration: EudraCT 2012-005530-11 and NCT 02147548 ∗ Correspondence to: Department of medical Pharmacology, Faculty of Medicine, 1 place Verdun, 59045 Lille, France.
    [Show full text]
  • Models of Insomnia Michael Perlis, Paul Shaw, Georgina Cano, and Colin Espie 78
    Chapter Models of Insomnia Michael Perlis, Paul Shaw, Georgina Cano, and Colin Espie 78 Up until the late 1990s there were only two models regard- history. A simple conditioning history, wherein a stimulus ing the etiology and pathophysiology of insomnia. The is always paired with a single behavior, yields a high prob- relative lack of theoretical perspectives was due to at least ability that the stimulus will yield only one response. A three factors. First, the widespread conceptualization of complex conditioning history, wherein a stimulus is paired insomnia as owing directly to hyperarousal may have made with a variety of behaviors, yields a low probability that it appear that further explanation was not necessary. the stimulus will yield only one response. In persons with Second, the long-time characterization of insomnia as a insomnia, the normal cues associated with sleep (e.g., bed, symptom carried with it the clear implication that insom- bedroom, bedtime, etc.) are often paired with activities nia was not itself worth modeling as a disorder or disease other than sleep. For instance, in an effort to cope with state. Third, for those inclined toward theory, the accep- insomnia, the patient might spend a large amount of time tance of the behavioral models (i.e., the 3P behavioral in the bed and bedroom awake and engaging in activities model and the stimulus control model1,2), and the treat- other than sleep. The coping behavior appears to the ments that were derived from them, might have had the patient to be both reasonable (e.g., staying in bed at least untoward effect of discouraging the development of alter- permits the patients to rest) and reasonably successful native or elaborative models.
    [Show full text]
  • UNDERSTANDING PHARMACOLOGY of ANTIEPILEPTIC DRUGS: Content
    UNDERSTANDING PHARMACOLOGY OF ANTIEPILEPTIC DRUGS: PK/PD, SIDE EFFECTS, DRUG INTERACTION THANARAT SUANSANAE, BPharm, BCPP, BCGP Assistance Professor of Clinical Pharmacy Faculty of Pharmacy, Mahidol University Content Mechanism of action Pharmacokinetic Adverse effects Drug interaction 1 Epileptogenesis Neuronal Network Synaptic Transmission Stafstrom CE. Pediatr Rev 1998;19:342‐51. 2 Two opposing signaling pathways for modulating GABAA receptor positioning and thus the excitatory/inhibitory balance within the brain Bannai H, et al. Cell Rep 2015. doi: 10.1016/j.celrep.2015.12.002 Introduction of AEDs in the World (US FDA Registration) Mechanism of action Pharmacokinetic properties Adverse effects Potential to develop drug interaction Formulation and administration Rudzinski LA, et al. J Investig Med 2016;64:1087‐101. 3 Importance of PK/PD of AEDs in Clinical Practice Spectrum of actions Match with seizure type Combination regimen Dosage regimen Absorption Distribution Metabolism Elimination Drug interactions ADR (contraindications, cautions) Mechanisms of Neuronal Excitability Voltage sensitive Na+ channels Voltage sensitive Ca2+ channels Voltage sensitive K+ channel Receptor‐ion channel complex Excitatory amino acid receptor‐cation channel complexes • Glutamate • Aspartate GABA‐Cl‐ channel complex 4 Mechanism of action of clinically approved anti‐seizure drugs Loscher W, et al. CNS Drugs 2016;30:1055‐77. Summarize Mechanisms of Action of AEDs AED Inhibition of Increase in Affinity to Blockade of Blockade of Activation of Other glutamate GABA level GABAA sodium calcium potassium excitation receptor channels channels channels Benzodiazepines + Brivaracetam + + Carbamazepine + + (L) Eslicarbazepine + Ethosuximide + (T) Felbamate +(NMDA) + + + + (L) + Gabapentin + (N, P/Q) Ganaxolone + Lacosamide + Lamotrigine + + + + (N, P/Q, R, T) + inh. GSK3 Levetiracetam + + (N) SV2A, inh.
    [Show full text]
  • WO 2007/109289 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date PCT (10) International Publication Number 27 September 2007 (27.09.2007) WO 2007/109289 Al (51) International Patent Classification: (74) Agents: INSOGNA, Anthony, M. et al; Jones Day, 222 C07D 265/14 (2006.01) A61P 25/00 (2006.01) East 41st Street, New York, NY 10017-6702 (US). A61K 31/535 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: kind of national protection available): AE, AG, AL, AM, PCT/US2007/006959 AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY,BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, (22) International Filing Date: 20 March 2007 (20.03.2007) FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, (25) Filing Language: English LS, LT, LU, LY,MA, MD, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, (26) Publication Language: English RU, SC, SD, SE, SG, SK, SL, SM, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW (30) Priority Data: 60/784,513 20 March 2006 (20.03.2006) US (84) Designated States (unless otherwise indicated, for every (71) Applicant (for all designated States except US): XYTIS kind of regional protection available): ARIPO (BW, GH, INC. [US/US]; 101 Theory Suite 100, Irvine, CA 92617 GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (US).
    [Show full text]
  • Premenstrual Dysphoric Disorder: How to Alleviate Her Suffering
    Premenstrual dysphoric disorder: How to alleviate her suffering Accurate diagnosis, tailored treatments can greatly improve women’s quality of life pproximately 75% of women experience a premen- strual change in emotional or physical symptoms Acommonly referred to as premenstrual syndrome (PMS). These symptoms—including increased irritability, tension, depressed mood, and somatic complaints such as breast tenderness and bloating—often are mild to moder- ate and cause minimal distress.1 However, approximately 3% to 9% of women experience moderate to severe premen- strual mood symptoms that meet criteria for premenstrual dysphoric disorder (PMDD).2 PMDD includes depressed or labile mood, anxiety, irri- tability, anger, insomnia, difficulty concentrating, and other © IMAGES.COM/CORBIS symptoms that occur exclusively during the 2 weeks before menses and cause significant deterioration in daily func- Laura Wakil, MD tioning. Women with PMDD use general and mental health Third-Year Psychiatry Resident services more often than women without the condition.3 Samantha Meltzer-Brody, MD, MPH They may experience impairment in marital and parental Director, Perinatal Psychiatry Program relationships as severe as that experienced by women with University of North Carolina Center for Women’s 2 Mood Disorders recurrent or chronic major depression. PMDD often responds to treatment. Unfortunately, Susan Girdler, PhD Director, UNC Stress and Health Research Program many women with PMDD do not seek treatment, and up Menstrually Related Mood Disorders Program to 90% may go undiagnosed.4 In this article, we review the University of North Carolina Center for Women’s prevalence, etiology, diagnosis, and treatment of PMDD. Mood Disorders • • • • Department of Psychiatry A complex disorder University of North Carolina at Chapel Hill A distinguishing characteristic of PMDD is the timing of Chapel Hill, NC symptom onset.
    [Show full text]
  • Screening of 300 Drugs in Blood Utilizing Second Generation
    Forensic Screening of 300 Drugs in Blood Utilizing Exactive Plus High-Resolution Accurate Mass Spectrometer and ExactFinder Software Kristine Van Natta, Marta Kozak, Xiang He Forensic Toxicology use Only Drugs analyzed Compound Compound Compound Atazanavir Efavirenz Pyrilamine Chlorpropamide Haloperidol Tolbutamide 1-(3-Chlorophenyl)piperazine Des(2-hydroxyethyl)opipramol Pentazocine Atenolol EMDP Quinidine Chlorprothixene Hydrocodone Tramadol 10-hydroxycarbazepine Desalkylflurazepam Perimetazine Atropine Ephedrine Quinine Cilazapril Hydromorphone Trazodone 5-(p-Methylphenyl)-5-phenylhydantoin Desipramine Phenacetin Benperidol Escitalopram Quinupramine Cinchonine Hydroquinine Triazolam 6-Acetylcodeine Desmethylcitalopram Phenazone Benzoylecgonine Esmolol Ranitidine Cinnarizine Hydroxychloroquine Trifluoperazine Bepridil Estazolam Reserpine 6-Monoacetylmorphine Desmethylcitalopram Phencyclidine Cisapride HydroxyItraconazole Trifluperidol Betaxolol Ethyl Loflazepate Risperidone 7(2,3dihydroxypropyl)Theophylline Desmethylclozapine Phenylbutazone Clenbuterol Hydroxyzine Triflupromazine Bezafibrate Ethylamphetamine Ritonavir 7-Aminoclonazepam Desmethyldoxepin Pholcodine Clobazam Ibogaine Trihexyphenidyl Biperiden Etifoxine Ropivacaine 7-Aminoflunitrazepam Desmethylmirtazapine Pimozide Clofibrate Imatinib Trimeprazine Bisoprolol Etodolac Rufinamide 9-hydroxy-risperidone Desmethylnefopam Pindolol Clomethiazole Imipramine Trimetazidine Bromazepam Felbamate Secobarbital Clomipramine Indalpine Trimethoprim Acepromazine Desmethyltramadol Pipamperone
    [Show full text]
  • Possible Modulation of Neurobehavioural Patterns by Anxiolytics Drugs
    Zaved Ahmed Khan et al. / International Journal of Pharma Sciences and Research (IJPSR) Vol.1(11), 2010, 457-464 Possible modulation of neurobehavioural patterns by anxiolytics drugs Zaved Ahmed Khan ,FICER (Corresponding Author) Assistant Professor Medical Biotechnology Division School of Biosciences and Technology, VIT University, Vellore-632014 TN, India Dr Asit Ranjan Ghosh Professor Medical Biotechnology Division School of Biosciences and Technology, VIT University, Vellore-632014 TN, India ABSTRACT Stress is very common and affects as many as one in eight every people in their teen years. Depression, which is common form of stress related disorder affects people of every color, race, economic status, or age. However, it does seem to affect more females than males during adolescence and adulthood. Stress affects mind, body, and behavior in many ways. The signs and symptoms of stress vary from person to person, but all have the potential to harm our health, emotional wellbeing, and relationships with others. The stress response of the body is meant to protect and support us in maintaining stability. Our body is constantly adjusting to its surroundings. When a physical or mental event threatens this equilibrium, we react to it. Anxiety is characterized by a persistent and disproportionate fear unrelated to any genuine risk. It can increase to an extent that may interfere with even normal routine of life and person may feel apprehensive regarding happenings of normal things in life. The present paper discusses anti-anxiety potential of 15 anxiolytics with emphasis on their pre-clinical and clinical reports.majority of drugs have been found to be acting through modulation of serotonin and gamma butyric acid (GABA) neurotransmitters.
    [Show full text]
  • Stresam® Summary of Product Characteristics
    SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT STRESAM®, capsule 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Active ingredient: Etifoxine hydrochloride ..................................................................... 50 mg For excipients: see 6.1 3. PHARMACEUTICAL FORM Capsule (blue and white). 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Psychosomatic manifestations of anxiety such as autonomic dystonia, notably of a cardiovascular nature. 4.2 Posology and method of administration Posology Usually 3 to 4 capsules a day, taken as 2 or 3 divided doses. Treatment duration : a few days to a few weeks. Method of administration Swallow the capsules with a little amount of water. 4.3 Contraindications - states of shock, - severely impaired liver and/or renal function, - myasthenia. 4.4 Special warnings and special precautions for use Warning Because of the presence of lactose, this medicine is contraindicated in patients with congenital galactosemia, glucose and galactose malabsorption syndrome or lactase deficit. Precautions Because of risks of reciprocal potentialisation: - combination with central depressants must be prescribed cautiously, - simultaneous intake of alcoholic drinks is inadvisable. 4.5 Interactions with other medicinal products and other forms of interaction INADVISABLE COMBINATIONS + ALCOHOL : Alcohol increases the sedative effect of these substances. Impaired alertness may make vehicle driving and machinery operation dangerous. Avoid alcoholic drinks and medicines containing alcohol. COMBINATIONS
    [Show full text]
  • Social Anxiety, Cortisol, and Early-Stage Friendship
    J S P R Article Journal of Social and Personal Relationships Social anxiety, cortisol, 2019, Vol. 36(7) 1954–1974 ª The Author(s) 2018 Article reuse guidelines: and early-stage friendship sagepub.com/journals-permissions DOI: 10.1177/0265407518774915 journals.sagepub.com/home/spr Sarah Ketay1, Keith M. Welker2, Lindsey A. Beck3, Katherine R. Thorson4, and Richard B. Slatcher5 Abstract Socially anxious people report less closeness to others, but very little research has examined how social anxiety is related to closeness in real-time social interactions. The present study investigated social anxiety, closeness, and cortisol reactivity in zero-acquaintance interactions between 84 same-sex dyads (168 participants). Dyads engaged in either a high or low self-disclosure discussion task and completed self- report measures of closeness and desired closeness post-task. Salivary cortisol was collected before, during, and after the self-disclosure task. Multilevel models indi- cated that in the high self-disclosure condition, individuals higher in social anxiety displayed flatter declines in cortisol than those lower in social anxiety; cortisol declines were not significantly related to social anxiety in the low self-disclosure condition. Further, across both conditions, individual’s social anxiety was associated with decreased levels of closeness and desired closeness, particularly when indi- viduals were paired with partners higher in social anxiety. These findings are dis- cussed in relation to previous work on hypothalamic–pituitary–adrenal function, social anxiety, and interpersonal closeness. Keywords Closeness, cortisol, friendship formation, self-disclosure, social anxiety 1 University of Hartford, USA 2 University of Massachusetts Boston, USA 3 Emerson College, USA 4 New York University, USA 5 Wayne State University, USA Corresponding author: Sarah Ketay, University of Hartford, 200 Bloomfield Avenue, West Hartford, CT 06117, USA.
    [Show full text]