Phencyclidine (PCP) Is a Dissociative Anesthetic
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Acetadote (Acetylcysteine) Injection Is Available As a 20% Solution in 30 Ml (200Mg/Ml) Single Dose Glass Vials
NDA 21-539/S-004 Page 3 Acetadote® (acetylcysteine) Injection Package Insert NDA 21-539/S-004 Page 4 RX ONLY PRESCRIBING INFORMATION ACETADOTE® (acetylcysteine) Injection For Intravenous Use DESCRIPTION Acetylcysteine injection is an intravenous (I.V.) medication for the treatment of acetaminophen overdose. Acetylcysteine is the nonproprietary name for the N-acetyl derivative of the naturally occurring amino acid, L-cysteine (N-acetyl-L-cysteine, NAC). The compound is a white crystalline powder, which melts in the range of 104° to 110°C and has a very slight odor. The molecular formula of the compound is C5H9NO3S, and its molecular weight is 163.2. Acetylcysteine has the following structural formula: H CH3 N SH O COOH Acetadote is supplied as a sterile solution in vials containing 20% w/v (200 mg/mL) acetylcysteine. The pH of the solution ranges from 6.0 to 7.5. Acetadote contains the following inactive ingredients: 0.5 mg/mL disodium edetate, sodium hydroxide (used for pH adjustment), and Sterile Water for Injection, USP. CLINICAL PHARMACOLOGY Acetaminophen Overdose: Acetaminophen is absorbed from the upper gastrointestinal tract with peak plasma levels occurring between 30 and 60 minutes after therapeutic doses and usually within 4 hours following an overdose. It is extensively metabolized in the liver to form principally the sulfate and glucoronide conjugates which are excreted in the urine. A small fraction of an ingested dose is metabolized in the liver by isozyme CYP2E1 of the cytochrome P-450 mixed function oxidase enzyme system to form a reactive, potentially toxic, intermediate metabolite. The toxic metabolite preferentially conjugates with hepatic glutathione to form nontoxic cysteine and mercapturic acid derivatives, which are then excreted by the kidney. -
The Promise of N-Acetylcysteine in Neuropsychiatry
Review The promise of N-acetylcysteine in neuropsychiatry 1,2,3,4 5,6 1 1,2,4 Michael Berk , Gin S. Malhi , Laura J. Gray , and Olivia M. Dean 1 School of Medicine, Deakin University, Geelong, Victoria, Australia 2 Department of Psychiatry, University of Melbourne, Parkville, Victoria, Australia 3 Orygen Research Centre, Parkville, Victoria, Australia 4 The Florey Institute of Neuroscience and Mental Health, Victoria, Australia 5 Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, Australia 6 CADE Clinic, Department of Psychiatry, Level 5 Building 36, Royal North Shore Hospital, St Leonards, 2065, Australia N-Acetylcysteine (NAC) targets a diverse array of factors with the pathophysiology of a diverse range of neuropsy- germane to the pathophysiology of multiple neuropsy- chiatric disorders, including autism, addiction, depression, chiatric disorders including glutamatergic transmission, schizophrenia, bipolar disorder, and Alzheimer’s and Par- the antioxidant glutathione, neurotrophins, apoptosis, kinson’s diseases [3]. Determining precisely how NAC mitochondrial function, and inflammatory pathways. works is crucial both to understanding the core biology This review summarises the areas where the mecha- of these illnesses, and to opening the door to other adjunc- nisms of action of NAC overlap with known pathophysi- tive therapies operating on these pathways. The current ological elements, and offers a pre´ cis of current literature article will initially review the possible mechanisms of regarding the use of NAC in disorders including cocaine, action of NAC, and then critically appraise the evidence cannabis, and smoking addictions, Alzheimer’s and Par- that suggests it has efficacy in the treatment of neuropsy- kinson’s diseases, autism, compulsive and grooming chiatric disorders. -
(Acetylcysteine) Effervescent Tablets for Oral Solution Intratracheal Instillation Initial U.S
HIGHLIGHTS OF PRESCRIBING INFORMATION • See the Full Prescribing Information for instructions on how to use the These highlights do not include all the information needed to use nomogram to determine the need for loading and maintenance dosing. CETYLEV® safely and effectively. See full prescribing information for CETYLEV. Recommended Adult and Pediatric Dosage (2.3): • CETYLEV is for oral administration only; not for nebulization or CETYLEV (acetylcysteine) effervescent tablets for oral solution intratracheal instillation Initial U.S. Approval: 1963 • Loading dose: 140 mg/kg • Maintenance doses: 70 mg/kg repeated every 4 hours for a total of 17 ----------------------------INDICATIONS AND USAGE--------------------------- doses. CETYLEV is an antidote for acetaminophen overdose indicated to prevent or • lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of See Full Prescribing Information for weight-based dosage and preparation acetaminophen in patients with acute ingestion or from repeated and administration instructions. supratherapeutic ingestion. (1) Repeated Supratherapeutic Acetaminophen Ingestion (2.4): -----------------------DOSAGE AND ADMINISTRATION----------------------- • Obtain acetaminophen concentration and other laboratory tests to guide Pre-Treatment Assessment Following Acute Ingestion (2.1): treatment; Rumack-Matthew nomogram does not apply. Obtain a plasma or serum sample to assay for acetaminophen concentration at least 4 hours after ingestion. ----------------------DOSAGE FORMS AND STRENGTHS--------------------- -
A Randomized Placebo-Controlled Trial of N-Acetylcysteine for Cannabis Use Disorder in Adults
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Drug Alcohol Manuscript Author Depend. Author Manuscript Author manuscript; available in PMC 2018 August 01. Published in final edited form as: Drug Alcohol Depend. 2017 August 01; 177: 249–257. doi:10.1016/j.drugalcdep.2017.04.020. A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults Kevin M. Graya, Susan C. Sonnea, Erin A. McClurea, Udi E. Ghitzab, Abigail G. Matthewsc, Aimee L. McRae-Clarka, Kathleen M. Carrolld, Jennifer S. Pottere, Katharina Wiestf, Larissa J. Mooneyg, Albert Hassong, Sharon L. Walshh, Michelle R. Lofwallh, Shanna Babalonish, Robert W. Lindbladc, Steven Sparenborgb,†, Aimee Wahlec, Jacqueline S. Kingc, Nathaniel L. Bakera, Rachel L. Tomkoa, Louise F. Haynesa, Ryan G. Vandreyi, and Frances R. Levinj aMedical University of South Carolina, Charleston SC bNational Institute on Drug Abuse Center for the Clinical Trials Network, Rockville MD cThe Emmes Corporation, Rockville MD dYale University, New Haven CT Correspondence: Kevin M. Gray, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 67 President Street, MSC861, Charleston, SC USA 29425, Phone: (843) 792-6330, Fax: (843) 792-8206, [email protected]. †Retired Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. -
Lega Italiana Per La Lotta Contro La Malattia Di Parkinson Le Sindromi Extrapiramidali E Le Demenze
LIMPE lega italiana per la lotta contro la malattia di parkinson le sindromi extrapiramidali e le demenze Web site: http://www.parkinson-limpe.it/ XXIX National Congress Lecce 23–25 October 2002 Parkinson Parkinsonism Dementia: from Biotechnology to Medical Management SELECTED SHORT PAPERS Scientific Committee Bruno Bergamasco, Giovanni U. Corsini, Mario Manfredi, Stefano Ruggieri, Pierfranco Spano Secretariat LIMPE Viale dell’Università 30, 00185 Roma Tel. and Fax: +39-06-4455618 E-mail: [email protected] Neurol Sci (2003) 24:149–150 DOI 10.1007/s10072-003-0103-5 123I-Ioflupane/SPECT binding to to the dopamine transporter (DAT) may be better suited and provide more-accurate estimation of degeneration. Several striatal dopamine transporter (DAT) tracers that bind to DAT and utilize SPECT are available; uptake in patients with Parkinson’s they are all cocaine derivatives. The most widely used are disease, multiple system atrophy, and [123I]β-CIT and 123I-Ioflupane ([123I]FP-CIT) [3, 4]. The main advantage of 123I-Ioflupane is that a steady state allow- progressive supranuclear palsy ing SPECT imaging is reached 3 h after a single bolus injec- 1 2 1 tion of the radioligand, compared with the 18–24 h required A. Antonini (౧) • R. Benti • R. De Notaris 1 1 1 for [123I]β-CIT. Therefore DAT imaging with 123I-Ioflupane S. Tesei • A. Zecchinelli • G. Sacilotto 1 1 1 1 can be completed the same day. N. Meucci • M. Canesi • C. Mariani • G. Pezzoli 123 P. Gerundini2 Several studies have demonstrated the usefulness of I- 1 Centro per la malattia di Parkinson, Dipartimento di Ioflupane SPECT imaging in the diagnosis of parkinsonism. -
Delayed Dosing of Minocycline Plus N-Acetylcysteine Reduces Neurodegeneration in Distal Brain Regions and Restores Spatial Memor
Manuscript bioRxiv preprint doi: https://doi.org/10.1101/2021.03.28.437090; this version posted March 29, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Delayed dosing of minocycline plus N-acetylcysteine reduces neurodegeneration in distal brain regions and restores spatial memory after experimental traumatic brain injury Kristen Whitney 1,2, Elena Nikulina1, Syed N. Rahman1, Alisia Alexis1 and Peter J. Bergold1,2 1Department of Physiology and Pharmacology 2Program in Neural and Behavioral Science, School of Graduate Studies State University of New York-Downstate Health Sciences University, Brooklyn NY 11215 Corresponding Author: [email protected] Department of Physiology and Pharmacology, Box 29 State University of New York – Downstate Health Sciences University 450 Clarkson Avenue Brooklyn, NY 11215 Declarations of interest: none Abbreviations: CHI- closed head injury Contra- contralateral Ipsi- ipsilateral MAP2 -microtubule associated protein 2 MINO- minocycline MN12- MINO plus NAC first dosed 12 hours after injury MN72- MINO plus NAC first dosed 72 hours after injury NAC- N-acetylcysteine TBI- Traumatic brain injury 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.03.28.437090; this version posted March 29, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Multiple drugs to treat traumatic brain injury (TBI) have failed clinical trials. Most drugs lose efficacy as the time interval increases between injury and treatment onset. Insufficient therapeutic time window is a major reason underlying failure in clinical trials. -
Selective Knockdown of TASK3 Potassium Channel in Monoamine
Manuscript Click here to download Manuscript Fullana et al - TASK3.docx 1 Research Article – Molecular Neurobiology 2 3 Selective Knockdown of TASK3 Potassium Channel in Monoamine 4 Neurons: A New Therapeutic Approach for Depression 5 M Neus Fullana1,2,3*, Albert Ferrés-Coy1,2,3*, Jorge E Ortega3,4, Esther Ruiz-Bronchal1,2,3, Verónica 6 Paz1,2,3, J Javier Meana3,4, Francesc Artigas1,2,3 and Analia Bortolozzi1,2,3 7 8 1Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain 9 2Department of Neurochemistry and Neuropharmacology, IIBB-CSIC (Consejo Superior de 10 Investigaciones Científicas), Barcelona, Spain. 11 3Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain. 12 4Department of Pharmacology, University of Basque Country UPV/EHU and BioCruces Health 13 Research Institute, Bizkaia, Spain 14 15 NF* and AF-C* contributed equally to this work. 16 For correspondence: Analia Bortolozzi, Department of Neurochemistry and Neuropharmacology 17 (IIBB-CSIC), Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Rosello 161, 18 Barcelona 08036, Spain. Tel: +34 93638313 Fax: +34 933638301 E-mail: 19 [email protected] 20 21 22 23 Running title: Intranasal delivery of conjugated TASK3-siRNA 24 25 26 1 Abstract 2 Current pharmacological treatments for major depressive disorder (MDD) are severely compromised 3 by both slow action and limited efficacy. RNAi strategies have been used to evoke antidepressant-like 4 effects faster than classical drugs. Using small interfering RNA (siRNA), we herein show that TASK3 5 potassium channel knockdown in monoamine neurons induces antidepressant-like responses in mice. -
Minocycline Synergizes with N-Acetylcysteine and Improves Cognition and Memory Following Traumatic Brain Injury in Rats
Minocycline Synergizes with N-Acetylcysteine and Improves Cognition and Memory Following Traumatic Brain Injury in Rats Samah G. Abdel Baki, Ben Schwab, Margalit Haber, Andre´ A. Fenton, Peter J. Bergold* Departments of Physiology and Pharmacology, State University of New York-Downstate Medical Center, Brooklyn, New York, United States of America Abstract Background: There are no drugs presently available to treat traumatic brain injury (TBI). A variety of single drugs have failed clinical trials suggesting a role for drug combinations. Drug combinations acting synergistically often provide the greatest combination of potency and safety. The drugs examined (minocycline (MINO), N-acetylcysteine (NAC), simvastatin, cyclosporine A, and progesterone) had FDA-approval for uses other than TBI and limited brain injury in experimental TBI models. Methodology/Principal Findings: Drugs were dosed one hour after injury using the controlled cortical impact (CCI) TBI model in adult rats. One week later, drugs were tested for efficacy and drug combinations tested for synergy on a hierarchy of behavioral tests that included active place avoidance testing. As monotherapy, only MINO improved acquisition of the massed version of active place avoidance that required memory lasting less than two hours. MINO-treated animals, however, were impaired during the spaced version of the same avoidance task that required 24-hour memory retention. Co- administration of NAC with MINO synergistically improved spaced learning. Examination of brain histology 2 weeks after injury suggested that MINO plus NAC preserved white, but not grey matter, since lesion volume was unaffected, yet myelin loss was attenuated. When dosed 3 hours before injury, MINO plus NAC as single drugs had no effect on interleukin-1 formation; together they synergistically lowered interleukin-1 levels. -
As Sensitive Plasma Biomarkers of Oxidative Stress Received: 22 June 2018 Xiaoyun Fu1,2, Shelby A
www.nature.com/scientificreports OPEN Cysteine Disulfdes (Cys-ss-X) as Sensitive Plasma Biomarkers of Oxidative Stress Received: 22 June 2018 Xiaoyun Fu1,2, Shelby A. Cate1, Melissa Dominguez1, Warren Osborn1, Tahsin Özpolat 1, Accepted: 6 November 2018 Barbara A. Konkle1,2, Junmei Chen1 & José A. López1,2 Published: xx xx xxxx We developed a high-throughput mass spectrometry–based method to simultaneously quantify numerous small-molecule thiols and disulfdes in blood plasma. Application of this assay to analyze plasma from patients with known oxidative stress (sickle cell disease and sepsis) and from a patient with sickle cell disease treated with the antioxidant N-acetylcysteine suggests that cysteine disulfdes, in particular protein-bound cysteine, serve as sensitive plasma biomarkers for the extent of oxidative stress and efectiveness of antioxidant treatment. Oxidative stress accompanies a wide variety of diseases1, including sickle cell disease (SCD), HIV/AIDS, and rheumatoid arthritis, and antioxidant therapy is emerging as a pharmacological strategy for treating diseases in which oxidative stress is known or suspected to be elevated2. Te ability to measure oxidative stress quantitatively is important for understanding disease mechanisms and monitoring the efectiveness of antioxidant treatments. Among biomarkers of oxidative stress, the ratio of reduced glutathione (GSH) to glutathione disulfde (GSSG) is frequently measured in various cell types, owing to the millimolar intracellular concentrations of these glu- tathione species and the broad availability of assays for their measurement, including many that are commercially available1,3,4. Despite these advantages, GSH/GSSG is not well suited as a plasma biomarker of oxidative stress due to the low plasma concentrations of GSH species, which are usually in the low micromolar range, and the low sensitivity of the assays. -
N-Acetylcysteine As a Treatment for Addiction
12 N-Acetylcysteine as a Treatment for Addiction Jennifer E. Murray1,2,*, Jérôme Lacoste3 and David Belin2,4 1Department of Experimental Psychology, University of Cambridge, Cambridge, 2INSERM European Associated Laboratory, Psychobiology of Compulsive Habits, 3Unité de Recherche Clinique Intersectorielle, Centre Hospitalier Henri-Laborit, Poitiers, 4INSERM U1084 - LNEC & Université de Poitiers, AVENIR Team Psychobiology of Compulsive Disorders, Poitiers, 1,2UK 2,3,4France 1. Introduction Drug addiction is a chronic relapsing disorder characterized by compulsive use despite negative consequences and relapses even after years of abstinence (Leshner, 1997). Criteria put forth by the American Psychiatric Association (2000) for diagnosing drug addiction require at least three of the following symptoms associated with drug use: tolerance; withdrawal; a loss of control over drug intake; unsuccessful attempts to reduce intake; a significant amount of time spent acquiring, using, or recovering from the substance; reduced interest in social or work activities; and continued use despite awareness of adverse physical and psychological consequences (American Psychiatric Association, 2000). In the United States, 22.5 million people, or 8.9% of the population meets the criteria for substance dependence or abuse (Substance Abuse and Mental Health Services Administration, 2010), and in Europe, drug, and especially cocaine, use has been increasing over the last ten years in the general population, with a more pronounced trend in young individuals (EMCDDA, 2009), suggesting that cocaine addiction may continue to spread in western countries. Worldwide estimates suggest more than 8% of the population have an alcohol use disorder and more than 2% have an illicit drug use disorder (World Health Organization, 2010). -
Monoamine Reuptake Inhibitors in Parkinson's Disease
Hindawi Publishing Corporation Parkinson’s Disease Volume 2015, Article ID 609428, 71 pages http://dx.doi.org/10.1155/2015/609428 Review Article Monoamine Reuptake Inhibitors in Parkinson’s Disease Philippe Huot,1,2,3 Susan H. Fox,1,2 and Jonathan M. Brotchie1 1 Toronto Western Research Institute, Toronto Western Hospital, University Health Network, 399 Bathurst Street, Toronto, ON, Canada M5T 2S8 2Division of Neurology, Movement Disorder Clinic, Toronto Western Hospital, University Health Network, University of Toronto, 399BathurstStreet,Toronto,ON,CanadaM5T2S8 3Department of Pharmacology and Division of Neurology, Faculty of Medicine, UniversitedeMontr´ eal´ and Centre Hospitalier de l’UniversitedeMontr´ eal,´ Montreal,´ QC, Canada Correspondence should be addressed to Jonathan M. Brotchie; [email protected] Received 19 September 2014; Accepted 26 December 2014 Academic Editor: Maral M. Mouradian Copyright © 2015 Philippe Huot et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The motor manifestations of Parkinson’s disease (PD) are secondary to a dopamine deficiency in the striatum. However, the degenerative process in PD is not limited to the dopaminergic system and also affects serotonergic and noradrenergic neurons. Because they can increase monoamine levels throughout the brain, monoamine reuptake inhibitors (MAUIs) represent potential therapeutic agents in PD. However, they are seldom used in clinical practice other than as antidepressants and wake-promoting agents. This review article summarises all of the available literature on use of 50 MAUIs in PD. The compounds are divided according to their relative potency for each of the monoamine transporters. -
Male Anorgasmia: from “No” to “Go!”
Male Anorgasmia: From “No” to “Go!” Alexander W. Pastuszak, MD, PhD Assistant Professor Center for Reproductive Medicine Division of Male Reproductive Medicine and Surgery Scott Department of Urology Baylor College of Medicine Disclosures • Endo – speaker, consultant, advisor • Boston Scientific / AMS – consultant • Woven Health – founder, CMO Objectives • Understand what delayed ejaculation (DE) and anorgasmia are • Review the anatomy and physiology relevant to these conditions • Review what is known about the causes of DE and anorgasmia • Discuss management of DE and anorgasmia Definitions Delayed Ejaculation (DE) / Anorgasmia • The persistent or recurrent delay, difficulty, or absence of orgasm after sufficient sexual stimulation that causes personal distress Intravaginal Ejaculatory Latency Time (IELT) • Normal (median) à 5.4 minutes (0.55-44.1 minutes) • DE à mean IELT + 2 SD = 25 minutes • Incidence à 2-11% • Depends in part on definition used J Sex Med. 2005; 2: 492. Int J Impot Res. 2012; 24: 131. Ejaculation • Separate event from erection! • Thus, can occur in the ABSENCE of erection! Periurethral muscle Sensory input - glans (S2-4) contraction Emission Vas deferens contraction Sympathetic input (T12-L1) SV, prostate contraction Bladder neck contraction Expulsion Bulbocavernosus / Somatic input (S1-3) spongiosus contraction Projectile ejaculation J Sex Med. 2011; 8 (Suppl 4): 310. Neurochemistry Sexual Response Areas of the Brain • Pons • Nucleus paragigantocellularis Neurochemicals • Norepinephrine, serotonin: • Inhibit libido,