Effect of Ergotamine on Serotonin-Mediated Responses In
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Strategies for Managing Sexual Dysfunction Induced by Antidepressant Medication
King’s Research Portal DOI: 10.1002/14651858.CD003382.pub3 Document Version Publisher's PDF, also known as Version of record Link to publication record in King's Research Portal Citation for published version (APA): Taylor, M. J., Rudkin, L., Bullemor-Day, P., Lubin, J., Chukwujekwu, C., & Hawton, K. (2013). Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database of Systematic Reviews, (5). https://doi.org/10.1002/14651858.CD003382.pub3 Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rights Copyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights. •Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research. •You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. -
52Nd Annual Meeting
ACNP 52nd Annual Meeting Final Program December 8-12, 2013 The Westin Diplomat Resort & Spa Hollywood, Florida President: David A. Lewis, M.D. Program Committee Chair: Randy D. Blakely, Ph.D. Program Committee Co-Chair: Pat R. Levitt, Ph.D. This meeting is jointly sponsored by the Vanderbilt University School of Medicine Department of Psychiatry and the American College of Neuropsychopharmacology. Dear ACNP Members and Guests, It is a distinct pleasure to welcome you to the 2014 meeting of the American College of Neuropsychopharmacology! This 52nd annual meeting will again provide opportunities for the exercise of the College’s core values: the spirit of Collegiality, promoting in each other the best in science, training and service; participation in Community, pursuing together the goals of understanding the neurobiology of brain diseases and eliminating their burden on individuals and our society; and engaging in Celebration, taking the time to recognize and enjoy the contributions and accomplishments of our members and guests. Under the excellent leadership of Randy Blakely and Pat Levitt, the Program Committee has done a superb job in assembling an outstanding slate of scientific presentations. Based on membership feedback, the meeting schedule has been designed with the goals of achieving an optimal mix of topics and types of sessions, increasing the diversity of participating scientists and creating more time for informal interactions. The presentations will highlight both the breadth of the investigative interests of ACNP membership -
The Role of the Serotonergic System and the Effects of Antidepressants During Brain Development Examined Using in Vivo Pet Imaging and in Vitro Receptor Binding
From THE DEPARTMENT OF CLINICAL NEUROSCIENCE Karolinska Institutet, Stockholm, Sweden THE ROLE OF THE SEROTONERGIC SYSTEM AND THE EFFECTS OF ANTIDEPRESSANTS DURING BRAIN DEVELOPMENT EXAMINED USING IN VIVO PET IMAGING AND IN VITRO RECEPTOR BINDING Stal Saurav Shrestha Stockholm 2014 Cover Illustration: Voxel-wise analysis of the whole monkey brain using the PET radioligand, [11C]DASB showing persistent serotonin transporter upregulation even after more than 1.5 years of fluoxetine discontinuation. All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by Universitetsservice-AB © Stal Saurav Shrestha, 2014 ISBN 978-91-7549-522-4 Serotonergic System and Antidepressants During Brain Development To my family Amaze yourself ! Stal Saurav Shrestha, 2014 The Department of Clinical Neuroscience The role of the serotonergic system and the effects of antidepressants during brain development examined using in vivo PET imaging and in vitro receptor binding AKADEMISK AVHANDLING som för avläggande av medicine doktorsexamen vid Karolinska Institutet offentligen försvaras i CMM föreläsningssalen L8:00, Karolinska Universitetssjukhuset, Solna THESIS FOR DOCTORAL DEGREE (PhD) Stal Saurav Shrestha Date: March 31, 2014 (Monday); Time: 10 AM Venue: Center for Molecular Medicine Lecture Hall Floor 1, Karolinska Hospital, Solna Principal Supervisor: Opponent: Robert B. Innis, MD, PhD Klaus-Peter Lesch, MD, PhD National Institutes of Health University of Würzburg Department of NIMH Department -
Monoamine Depletion in Psychiatric and Healthy Populations
Molecular Psychiatry (2003) 8, 951–973 & 2003 Nature Publishing Group All rights reserved 1359-4184/03 $25.00 www.nature.com/mp FEATURE REVIEW Monoamine depletion in psychiatric and healthy populations: review L Booij1, AJW Van der Does1,2 and WJ Riedel3,4,5 1Department of Psychology, Leiden University, Leiden 2333 AK, The Netherlands; 2Department of Psychiatry, Leiden University, Leiden 2333 AK, The Netherlands; 3GlaxoSmithKline, Translational Medicine & Technology, Cambridge, UK; 4Department of Psychiatry, University of Cambridge, UK; 5Faculty of Psychology, Maastricht University, The Netherlands A number of techniques temporarily lower the functioning of monoamines: acute tryptophan depletion (ATD), alpha-methyl-para-tyrosine (AMPT) and acute phenylalanine/tyrosine deple- tion (APTD). This paper reviews the results of monoamine depletion studies in humans for the period 1966 until December 2002. The evidence suggests that all three interventions are specific, in terms of their short-term effects on one or two neurotransmitter systems, rather than on brain protein metabolism in general. The AMPT procedure is somewhat less specific, affecting both the dopamine and norepinephrine systems. The behavioral effects of ATD and AMPT are remarkably similar. Neither procedure has an immediate effect on the symptoms of depressed patients; however, both induce transient depressive symptoms in some remitted depressed patients. The magnitude of the effects, response rate and quality of response are also comparable. APTD has not been studied in recovered major depressive patients. Despite the similarities, the effects are distinctive in that ATD affects a subgroup of recently remitted patients treated with serotonergic medications, whereas AMPT affects recently remitted patients treated with noradrenergic medications. -
Original Article E€Ects of Serotonin 1A Agonist on Acute Spinal Cord Injury
Spinal Cord (2002) 40, 519 ± 523 ã 2002 International Spinal Cord Society All rights reserved 1362 ± 4393/02 $25.00 www.nature.com/sc Original Article Eects of serotonin 1A agonist on acute spinal cord injury Y Saruhashi*,1, Y Matsusue1 and S Hukuda2 1Department of Orthopedic Surgery, Shiga University of Medical Science, Otsu, Japan; 2Tane-daini Hospital, Osaka, Japan Study design: We evaluated the eects of serotonin (5-HT) agonists on in vitro models of spinal cord compressive injury. Evoked potentials in injured rat spinal cords (n=24) were recorded during perfusion with 5-HT agonists. Objectives: To evaluate the therapeutic eects of 5-HT agonists on the recovery of compound action potentials in injured spinal cords. Methods: Rat dorsal columns were isolated, placed in a chamber, and injured by extradural compression with a clip. Conducting action potentials were activated by supramaximal constant current electrical stimuli and recorded during perfusion with 5-HT agonists and antagonists. Results: After inducing compression injuries, mean action potential amplitudes were reduced to 33.9+5.4% of the pre-injury level. After 120 min of perfusion with Ringer's solution, the mean amplitudes recovered to 62.8+8.4% of the pre-injury level. At a concentration of 100 mM, perfusion with tandospirone (a 5-HT1A agonist) resulted in a signi®cantly greater recovery of mean action potential amplitudes at 2 h after the injury (86.2+6.9% of pre-injury value) as compared with the control Ringer's solution (62.8+8.4% of pre-injury value, P50.05). In contrast, quipazine (a 5-HT2A agonist) accelerated the decrease of amplitude (54.5+11.7% of pre-injury value). -
The Effects of Clonidine and Idazoxan on Cerebral Blood Flow in Rats Studied by Arterial Spin Labeling Magnetic Resonance Perfusion Imaging
The Effects of Clonidine and Idazoxan on Cerebral Blood Flow in Rats Studied by Arterial Spin Labeling Magnetic Resonance Perfusion Imaging X. Du1, H. Lei1 1State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics & Mathematics, Chinese Academy of Sciences, Wuhan, Hubei, China, People's Republic of Introduction Agonists of α2-adrenoceptors are known to produce many central and peripheral effects. For example, xylazine, a selective α2-adrenoceptors agonist, has been shown to cause region-dependent CBF decreases in rat [1]. Clonidine, an agonist for both α2-adrenergic receptor and imidazoline receptor, is a widely used drug for treating hypertension. Its effect on CBF, however, is not well understood. In this study, continuous arterial labeling (CASL) MR perfusion imaging was used to investigate the effects of clonidine and idazoxan, an antagonist for α2-adrenergic and imidazoline receptors, on CBF in rats. Materials and Methods Twelve male Sprague-Dawley rats, weighting 250-320 g, were used. After intubation, the rats were anesthetized by 1.0-1.5% isoflurane in a 70:30 N2O/O2 gas mixture. For each rat, bilateral femoral arteries and the right femoral vein were catheterized for monitoring blood gases and blood pressure, and for delivering drugs. Rectal temperature was maintained at 37.0-37.5 oC using a warm water pad. After measuring baseline CBF, the rats were divided into two groups. In the first group (n=7), clonidine (10 µg/kg, i.v.) was injected first, followed by idazoxan injection (300 µg/kg, i.v.) at 30 minutes later. Perfusion maps were obtained after administration of each drug. -
Antipsychotics
The Fut ure of Antipsychotic Therapy (page 7 in syllabus) Stepp,,hen M. Stahl, MD, PhD Adjunct Professor, Department of Psychiatry Universityyg of California, San Diego School of Medicine Honorary Visiting Senior Fellow, Cambridge University, UK Sppyonsored by the Neuroscience Education Institute Additionally sponsored by the American Society for the Advancement of Pharmacotherapy This activity is supported by an educational grant from Sunovion Pharmaceuticals Inc. Copyright © 2011 Neuroscience Education Institute. All rights reserved. Individual Disclosure Statement Faculty Editor / Presenter Stephen M. Stahl, MD, PhD, is an adjunct professor in the department of psychiatry at the University of California, San Diego School of Medicine, and an honorary visiting senior fellow at the University of Cambridge in the UK. Grant/Research: AstraZeneca, BioMarin, Dainippon Sumitomo, Dey, Forest, Genomind, Lilly, Merck, Pamlab, Pfizer, PGxHealth/Trovis, Schering-Plough, Sepracor/Sunovion, Servier, Shire, Torrent Consultant/Advisor: Advent, Alkermes, Arena, AstraZeneca, AVANIR, BioMarin, Biovail, Boehringer Ingelheim, Bristol-Myers Squibb, CeNeRx, Cypress, Dainippon Sumitomo, Dey, Forest, Genomind, Janssen, Jazz, Labopharm, Lilly, Lundbeck, Merck, Neuronetics, Novartis, Ono, Orexigen, Otsuka, Pamlab, Pfizer, PGxHealth/Trovis, Rexahn, Roche, Royalty, Schering-Plough, Servier, Shire, Solvay/Abbott, Sunovion/Sepracor, Valeant, VIVUS, Speakers Bureau: Dainippon Sumitomo, Forest, Lilly, Merck, Pamlab, Pfizer, Sepracor/Sunovion, Servier, Wyeth Copyright © 2011 Neuroscience Education Institute. All rights reserved. Learninggj Objectives • Differentiate antipsychotic drugs from each other on the basis of their pharmacological mechanisms and their associated therapeutic and side effects • Integrate novel treatment approaches into clinical practice according to best practices guidelines • Identify novel therapeutic options currently being researched for the treatment of schizophrenia Copyright © 2011 Neuroscience Education Institute. -
5-HT1A Receptor-Dependent Modulation of Emotional
www.nature.com/scientificreports OPEN 5-HT1A receptor-dependent modulation of emotional and neurogenic defcits elicited by Received: 8 May 2017 Accepted: 19 January 2018 prolonged consumption of alcohol Published: xx xx xxxx Arnauld Belmer 1,2, Omkar L. Patkar1,2, Vanessa Lanoue3 & Selena E. Bartlett 1,2 Repeated episodes of binge-like alcohol consumption produce anxiety, depression and various deleterious efects including alterations in neurogenesis. While the involvement of the serotonin receptor 1 A (5-HT1A) in the regulation of anxiety-like behavior and neurogenesis is well documented, its contribution to alcohol withdrawal-induced anxiety and alcohol-induced defcits in neurogenesis is less documented. Using the Drinking-In-the-Dark (DID) paradigm to model chronic long-term (12 weeks) binge-like voluntary alcohol consumption in mice, we show that the selective partial activation of 5-HT1A receptors by tandospirone (3 mg/kg) prevents alcohol withdrawal-induced anxiety in a battery of behavioral tests (marble burying, elevated-plus-maze, open-feld), which is accompanied by a robust decrease in binge-like ethanol intake (1 and 3 mg/kg). Furthermore, using triple immunolabelling of proliferation and neuronal diferentiation markers, we show that long-term DID elicits profound defcits in neurogenesis and neuronal fate specifcation in the dorsal hippocampus that are entirely reversed by a 2-week chronic treatment with the 5-HT1A partial agonist tandospirone (3 mg/kg/day). Together, our results confrm previous observations that 5-HT1A receptors play a pivotal role in alcohol drinking behavior and the associated emotional and neurogenic impairments, and suggest that 5-HT1A partial agonists represent a promising treatment strategy for alcohol abuse. -
Phd Thesis Project: Pharmacological and Toxicological Investigations of New Psychoactive Substances, Supervised by Prof
PHARMACOLOGICAL AND TOXICOLOGICAL INVESTIGATIONS OF NEW PSYCHOACTIVE SUBSTANCES Inauguraldissertation zur Erlangung der Würde eines Doktors der Philosophie vorgelegt der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel von Dino Lüthi aus Rüderswil, Bern Basel, 2018 Originaldokument gespeichert auf dem Dokumentenserver der Universität Basel edoc.unibas.ch Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung-Nicht kommerziell 4.0 International Lizenz (https://creativecommons.org/licenses/by-nc-sa/4.0/deed.de). Genehmigt von der Philosophisch-Naturwissenschaftlichen Fakultät auf Antrag von Prof. Stephan Krähenbühl, Prof. Matthias E. Liechti und Prof. Anne Eckert. Basel, den 26.06.2018 Prof. Martin Spiess Dekan der Philosophisch- Naturwissenschaftlichen Fakultät PHARMACOLOGICAL AND TOXICOLOGICAL INVESTIGATIONS OF NEW PSYCHOACTIVE SUBSTANCES “An adult must make his own decision as to whether or not he should expose himself to a specific drug, be it available by prescription or proscribed by law, by measuring the potential good and bad with his own personal yardstick.” ― Alexander Shulgin, Pihkal: A Chemical Love Story. PREFACE This thesis is split into a pharmacology part and a toxicology part. The pharmacology part consists of investigations on the monoamine transporter and receptor interactions of traditional and newly emerged drugs, mainly stimulants and psychedelics; the toxicology part consists of investigations on mechanisms of hepatocellular toxicity of synthetic cathinones. All research described in this thesis has been published in peer-reviewed journals, and was performed between October 2014 and June 2018 in the Division of Clinical Pharmacology and Toxicology at the Department of Biomedicine of the University Hospital Basel and University of Basel, and partly at the pRED Roche Innovation Center Basel at F. -
Dopamine D2 Receptors in the Cerebral Cortex
Proc. Nati. Acad. Sci. USA Vol. 86, pp. 6412-6416, August 1989 Neurobiology Dopamine D2 receptors in the cerebral cortex: Distribution and pharmacological characterization with [3Hlraclopride (raclopride binding/neostriatum/rat/monkey) MICHAEL S. LIDOW*t, PATRICIA S. GOLDMAN-RAKIC*, PASKO RAKIC*, AND ROBERT B. INNIS*f Section of *Neuroanatomy and tDepartment of Psychiatry, Yale University, School of Medicine, New Haven, CT 06510 Contributed by Pasko Rakic, May 17, 1989 ABSTRACT An apparent involvement of dopamine in the MATERIALS AND METHODS regulation of cognitive functions and the recognition of a widespread dopaminergic innervation of the cortex have fo- Tissue was obtained from three adult rhesus monkeys cused attention on the identity of cortical dopamine receptors. (Macaca mulatta): one male and two females. The animals However, only the presence and distribution of dopamine DI were anesthesized with sodium pentobarbital (40 mg/kg) and receptors in the cortex have been well documented. Compa- perfused with ice-cold phosphate-buffered saline followed by rable information on cortical D2 sites is lacking. We report here 0.1% paraformaldehyde (9; 15). The cerebral cortex and the results of binding studies in the cortex and neostriatum of neostriatum were rapidly removed and immersed in isopen- rat and monkey using the D2 selective antagonist [3H]raclo- tane at -700C for 5 min before storing at -800C until use. For pride. In both structures [3H]raclopride bound in a sodium- competition studies tissue was pooled from several neocor- dependent and saturable manner to a single population of sites tical areas. However, saturation studies were conducted on with pharmacological profiles of dopamine D2 receptors. -
Antidepressant Potential of Nitrogen-Containing Heterocyclic Moieties: an Updated Review
Review Article Antidepressant potential of nitrogen-containing heterocyclic moieties: An updated review Nadeem Siddiqui, Andalip, Sandhya Bawa, Ruhi Ali, Obaid Afzal, M. Jawaid Akhtar, Bishmillah Azad, Rajiv Kumar Department of ABSTRACT Pharmaceutical Chemistry, Depression is currently the fourth leading cause of disease or disability worldwide. Antidepressant is Faculty of Pharmacy, Jamia Hamdard approved for the treatment of major depression (including paediatric depression), obsessive-compulsive University, Hamdard disorder (in both adult and paediatric populations), bulimia nervosa, panic disorder and premenstrual Nagar, New Delhi - dysphoric disorder. Antidepressant is a psychiatric medication used to alleviate mood disorders, such as 110 062, India major depression and dysthymia and anxiety disorders such as social anxiety disorder. Many drugs produce an antidepressant effect, but restrictions on their use have caused controversy and off-label prescription a Address for correspondence: risk, despite claims of superior efficacy. Our current understanding of its pathogenesis is limited and existing Dr. Sandhya Bawa, E-mail: sandhyabawa761@ treatments are inadequate, providing relief to only a subset of people suffering from depression. Reviews of yahoo.com literature suggest that heterocyclic moieties and their derivatives has proven success in treating depression. Received : 08-02-11 Review completed : 15-02-11 Accepted : 17-02-11 KEY WORDS: Antidepressant, depression, heterocyclic epression is a chronic, recurring and potentially life- monoamine oxidase inhibitors (MAOIs, e.g. Nardil®) tricyclic D threatening illness that affects up to 20% of the population antidepressants (TCAs, e.g. Elavil). They increases the synaptic across the globe.[1] The etiology of the disease is suboptimal concentration of either two (5-HT and NE) or all three (5-HT, concentrations of the monoamine neurotransmitters serotonin NE and dopamine (DA)) neurotransmitters. -
Psychosis and Schizophrenia in Clinical Practice Psychosis in Practice
11/1/2017 Psychosis and Schizophrenia in Clinical Practice David Pickar, MD Adjunct Professor Johns Hopkins USUHS Psychosis in Practice • Schizophrenia • Mania • Depression • Brief Psychotic Episodes • Substance Abuse • FASD and other Neurodevelopment Disorders 1 11/1/2017 Schizophrenia • Late Adolescent/Early Adult Age of Onset • Life-Long Condition and Chronic Medication – Typical Antipsychotic drugs – introduced in 50’s -60’s – Atypical Antipsychotic drugs – introduced in later 80’s 90’s – Clozapine is the only ADP with demonstrated superiority – Market For Antipsychotic Drugs : Peak $16B /year US • 1% of World Population • Common “Complex” Disorder – Pathophysiology – Genetics – Variable Phenotype • Positive and Negative Symptoms and Cognitive Deficits • 10% Completed Suicide Prevalence and Treatment Rates • 8.1 million adults with schizophrenia or bipolar disorder mental illness (3.3% of the population)+ • 5.4 million – approximate number with severe bipolar disorder (2.2% of the population), 51% untreated+ • 2.7 million – approximate number with schizophrenia (1.1% of the population), 40% untreated+ • 3.9 million – approximate number untreated seriously mentally ill patients in any given year (1.6% of the population)+ 2 11/1/2017 Positive and Negative Symptom Scale (PANSS) Positive Symptoms • 7 Items, (minimum score = 7, maximum score = 49) • Delusions • Conceptual disorganization • Hallucinations • Excitement • Grandiosity • Suspiciousness/persecution • Hostility 3 11/1/2017 PANSS Negative Symptoms • 7 Items, (minimum score = 7,