Memantine Derivatives As Multitarget Agents in Alzheimer's Disease
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Dextromethorphan Attenuates Sensorineural Hearing Loss in an Animal Model and Population-Based Cohort Study
International Journal of Environmental Research and Public Health Article Dextromethorphan Attenuates Sensorineural Hearing Loss in an Animal Model and Population-Based Cohort Study Hsin-Chien Chen 1,* , Chih-Hung Wang 1,2 , Wu-Chien Chien 3,4 , Chi-Hsiang Chung 3,4, Cheng-Ping Shih 1, Yi-Chun Lin 1,2, I-Hsun Li 5,6, Yuan-Yung Lin 1,2 and Chao-Yin Kuo 1 1 Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan; [email protected] (C.-H.W.); [email protected] (C.-P.S.); [email protected] (Y.-C.L.); [email protected] (Y.-Y.L.); [email protected] (C.-Y.K.) 2 Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan 3 School of Public Health, National Defense Medical Center, Taipei 114, Taiwan; [email protected] (W.-C.C.); [email protected] (C.-H.C.) 4 Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan 5 Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan; [email protected] 6 School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan * Correspondence: [email protected]; Tel.: +886-2-8792-7192; Fax: +886-2-8792-7193 Received: 31 July 2020; Accepted: 28 August 2020; Published: 31 August 2020 Abstract: The effect of dextromethorphan (DXM) use in sensorineural hearing loss (SNHL) has not been fully examined. We conducted an animal model and nationwide retrospective matched-cohort study to explore the association between DXM use and SNHL. -
Hallucinogens - LSD, Peyote, Psilocybin, and PCP
Hallucinogens - LSD, Peyote, Psilocybin, and PCP Hallucinogenic compounds found in some • Psilocybin (4-phosphoryloxy-N,N- plants and mushrooms (or their extracts) dimethyltryptamine) is obtained from have been used—mostly during religious certain types of mushrooms that are rituals—for centuries. Almost all indigenous to tropical and subtropical hallucinogens contain nitrogen and are regions of South America, Mexico, and classified as alkaloids. Many hallucinogens the United States. These mushrooms have chemical structures similar to those of typically contain less than 0.5 percent natural neurotransmitters (e.g., psilocybin plus trace amounts of acetylcholine-, serotonin-, or catecholamine- psilocin, another hallucinogenic like). While the exact mechanisms by which substance. hallucinogens exert their effects remain • PCP (phencyclidine) was developed in unclear, research suggests that these drugs the 1950s as an intravenous anesthetic. work, at least partially, by temporarily Its use has since been discontinued due interfering with neurotransmitter action or to serious adverse effects. by binding to their receptor sites. This DrugFacts will discuss four common types of How Are Hallucinogens Abused? hallucinogens: The very same characteristics that led to • LSD (d-lysergic acid diethylamide) is the incorporation of hallucinogens into one of the most potent mood-changing ritualistic or spiritual traditions have also chemicals. It was discovered in 1938 led to their propagation as drugs of abuse. and is manufactured from lysergic acid, Importantly, and unlike most other drugs, which is found in ergot, a fungus that the effects of hallucinogens are highly grows on rye and other grains. variable and unreliable, producing different • Peyote is a small, spineless cactus in effects in different people at different times. -
Galantamine Potentiates the Neuroprotective Effect of Memantine Against NMDA-Induced Excitotoxicity Joao~ P
Galantamine potentiates the neuroprotective effect of memantine against NMDA-induced excitotoxicity Joao~ P. Lopes1, Glauco Tarozzo1, Angelo Reggiani1, Daniele Piomelli1,2 & Andrea Cavalli1,3 1D3 – Drug Discovery and Development Department, Istituto Italiano di Tecnologia, Via Morego, 16163, Genova, Italy 2Departments of Anatomy and Neurobiology and Biological Chemistry, University of California, Irvine, CA, 92697-4621 3Department of Pharmacy and Biotechnologies, Alma Mater Studiorum, Bologna University, Via Belmeloro, 40126, Bologna, Italy Keywords Abstract Alzheimer’s disease, drug combination, N NMDA neurotoxicity, NR2B, The combination of memantine, an -methyl-D-aspartate (NMDA) receptor polypharmacology, primary cortical neurons antagonist, with an acetylcholinesterase inhibitor (AChEI) is the current stan- dard of care in Alzheimer’s disease (AD). Galantamine, an AChEI currently Correspondence marketed for the treatment of AD, exerts memory-enhancing and neuroprotec- Andrea Cavalli, D3 – Drug Discovery and tive effects via activation of nicotinic acetylcholine receptors (nAChRs). Here, Development Department, Istituto Italiano we investigated the neuroprotective properties of galantamine in primary cul- di Tecnologia – Via Morego, 30, 16163 tures of rat cortical neurons when given alone or in combination with meman- Genova, Italy. Tel: +39 010 71781530; Fax: +39 010 tine. In agreement with previous findings, we found that memantine was fully 71781228; E-mail: [email protected] effective in reversing NMDA toxicity at concentrations of 2.5 and 5 lmol/L. Galantamine also completely reversed NMDA toxicity at a concentration of Funding Information 5 lmol/L. The a7 and a4b2 nAChR antagonists, methyllycaconitine, and dihy- No funding information provided. dro-b-erythroidine blocked the neuroprotective effect of galantamine, demon- strating the involvement of nAChRs. -
Molecular Modeling of Major Tobacco Alkaloids in Mainstream Cigarette Smoke Caren Kurgat, Joshua Kibet* and Peter Cheplogoi
Kurgat et al. Chemistry Central Journal (2016) 10:43 DOI 10.1186/s13065-016-0189-5 RESEARCH ARTICLE Open Access Molecular modeling of major tobacco alkaloids in mainstream cigarette smoke Caren Kurgat, Joshua Kibet* and Peter Cheplogoi Abstract Background: Consensus of opinion in literature regarding tobacco research has shown that cigarette smoke can cause irreparable damage to the genetic material, cell injury, and general respiratory landscape. The alkaloid family of tobacco has been implicated is a series of ailments including addiction, mental illnesses, psychological disorders, and cancer. Accordingly, this contribution describes the mechanistic degradation of major tobacco alkaloids including the widely studied nicotine and two other alkaloids which have received little attention in literature. The principal focus is to understand their energetics, their environmental fate, and the formation of intermediates considered harmful to tobacco consumers. Method: The intermediate components believed to originate from tobacco alkaloids in mainstream cigarette smoke were determined using as gas-chromatography hyphenated to a mass spectrometer fitted with a mass selective detector (MSD) while the energetics of intermediates were conducted using the density functional theory framework (DFT/B3LYP) using the 6-31G basis set. Results: The density functional theory calculations conducted using B3LYP correlation function established that the scission of the phenyl C–C bond in nicotine and β-nicotyrine, and C–N phenyl bond in 3,5-dimethyl-1-phenylpyrazole were respectively 87.40, 118.24 and 121.38 kcal/mol. The major by-products from the thermal degradation of nicotine, β-nicotyrine and 3,5-dimethyl-1-phenylpyrazole during cigarette smoking are predicted theoretically to be pyridine, 3-methylpyridine, toluene, and benzene. -
Hallucinogens and Dissociative Drugs
Long-Term Effects of Hallucinogens See page 5. from the director: Research Report Series Hallucinogens and dissociative drugs — which have street names like acid, angel dust, and vitamin K — distort the way a user perceives time, motion, colors, sounds, and self. These drugs can disrupt a person’s ability to think and communicate rationally, or even to recognize reality, sometimes resulting in bizarre or dangerous behavior. Hallucinogens such as LSD, psilocybin, peyote, DMT, and ayahuasca cause HALLUCINOGENS AND emotions to swing wildly and real-world sensations to appear unreal, sometimes frightening. Dissociative drugs like PCP, DISSOCIATIVE DRUGS ketamine, dextromethorphan, and Salvia divinorum may make a user feel out of Including LSD, Psilocybin, Peyote, DMT, Ayahuasca, control and disconnected from their body PCP, Ketamine, Dextromethorphan, and Salvia and environment. In addition to their short-term effects What Are on perception and mood, hallucinogenic Hallucinogens and drugs are associated with psychotic- like episodes that can occur long after Dissociative Drugs? a person has taken the drug, and dissociative drugs can cause respiratory allucinogens are a class of drugs that cause hallucinations—profound distortions depression, heart rate abnormalities, and in a person’s perceptions of reality. Hallucinogens can be found in some plants and a withdrawal syndrome. The good news is mushrooms (or their extracts) or can be man-made, and they are commonly divided that use of hallucinogenic and dissociative Hinto two broad categories: classic hallucinogens (such as LSD) and dissociative drugs (such drugs among U.S. high school students, as PCP). When under the influence of either type of drug, people often report rapid, intense in general, has remained relatively low in emotional swings and seeing images, hearing sounds, and feeling sensations that seem real recent years. -
The Effects of Dextromethorphan on Response Acquisition with Delayed Reinforcement
Western Michigan University ScholarWorks at WMU Dissertations Graduate College 6-2005 The Effects of Dextromethorphan on Response Acquisition with Delayed Reinforcement Thomas B. Morgan Western Michigan University Follow this and additional works at: https://scholarworks.wmich.edu/dissertations Part of the Mental and Social Health Commons, and the Psychology Commons Recommended Citation Morgan, Thomas B., "The Effects of Dextromethorphan on Response Acquisition with Delayed Reinforcement" (2005). Dissertations. 1050. https://scholarworks.wmich.edu/dissertations/1050 This Dissertation-Open Access is brought to you for free and open access by the Graduate College at ScholarWorks at WMU. It has been accepted for inclusion in Dissertations by an authorized administrator of ScholarWorks at WMU. For more information, please contact [email protected]. THE EFFECTS OF DEXTROMETHORPHAN ON RESPONSE ACQUISITION WITH DELAYED REINFORCEMENT by Thomas B. Morgan A Dissertation Submitted to the Faculty of The Graduate College in partial fulfillment of the requirements for the Degree of Doctor of Philosophy Department of Psychology Western Michigan University Kalamazoo, Michigan June 2005 THE EFFECTS OF DEXTROMETHORPHAN ON RESPONSE ACQUISITION WITH DELAYED REINFORCEMENT Thomas B. Morgan, Ph. D. Western Michigan University, 2005 The current study examined in 2-h sessions the effects of intraperitoneal injec- tions of dextromethorphan (DM) (0.0, 40.0, 60.0, and 80.0 mg/kg) on the acquisition of lever-press responding in rats that were exposed to a two-lever procedure in which responses on the reinforcement lever (RL) were reinforced with food after a 15-s re- setting delay and responses on the cancellation lever cancelled a scheduled reinforcer. -
A Steroid Modulatory Domain on NR2B Controls N-Methyl-D-Aspartate Receptor Proton Sensitivity
A steroid modulatory domain on NR2B controls N-methyl-D-aspartate receptor proton sensitivity Ming-Kuei Jang†, Dale F. Mierke‡, Shelley J. Russek†, and David H. Farb†§ †Laboratory of Molecular Neurobiology, Department of Pharmacology, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118; and ‡Department of Molecular Pharmacology, Division of Biology and Medicine, and Department of Chemistry, Brown University, Providence, RI 02912 Edited by Erminio Costa, University of Illinois, Chicago, IL, and approved April 5, 2004 (received for review March 15, 2004) N-methyl-D-aspartate (NMDA) receptor function is modulated by have been shown to regulate native NMDA receptors via distinct several endogenous molecules, including zinc, polyamines, pro- recognition sites; PS modulation is also not dependent on the tons, and sulfated neurosteroids. Zinc, polyamines, and phenyleth- redox state of the receptor (24). To define the mode of action of anolamines exert their respective modulatory effects by exacer- PS and to determine structural components at the NMDA bating or relieving tonic proton inhibition. Here, we report that receptor that are critical for PS modulation, we took advantage pregnenolone sulfate (PS) uses a unique mechanism for enhance- of our previous finding that PS differentially modulates activity ment of NMDA receptor function that is independent of the proton of recombinant receptors containing different NR2 subunits sensor. We identify a steroid modulatory domain, SMD1, on the (25). PS potentiates the response of recombinant NMDA re- NMDA receptor NR2B subunit that is critical for both PS enhance- ceptors containing NR2A or NR2B subunits, while inhibiting the ment and proton sensitivity. This domain includes the J͞K helices response of receptors containing NR2C or NR2D subunits. -
Long-Lasting Analgesic Effect of the Psychedelic Drug Changa: a Case Report
CASE REPORT Journal of Psychedelic Studies 3(1), pp. 7–13 (2019) DOI: 10.1556/2054.2019.001 First published online February 12, 2019 Long-lasting analgesic effect of the psychedelic drug changa: A case report GENÍS ONA1* and SEBASTIÁN TRONCOSO2 1Department of Anthropology, Philosophy and Social Work, Universitat Rovira i Virgili, Tarragona, Spain 2Independent Researcher (Received: August 23, 2018; accepted: January 8, 2019) Background and aims: Pain is the most prevalent symptom of a health condition, and it is inappropriately treated in many cases. Here, we present a case report in which we observe a long-lasting analgesic effect produced by changa,a psychedelic drug that contains the psychoactive N,N-dimethyltryptamine and ground seeds of Peganum harmala, which are rich in β-carbolines. Methods: We describe the case and offer a brief review of supportive findings. Results: A long-lasting analgesic effect after the use of changa was reported. Possible analgesic mechanisms are discussed. We suggest that both pharmacological and non-pharmacological factors could be involved. Conclusion: These findings offer preliminary evidence of the analgesic effect of changa, but due to its complex pharmacological actions, involving many neurotransmitter systems, further research is needed in order to establish the specific mechanisms at work. Keywords: analgesic, pain, psychedelic, psychoactive, DMT, β-carboline alkaloids INTRODUCTION effects of ayahuasca usually last between 3 and 5 hr (McKenna & Riba, 2015), but the effects of smoked changa – The treatment of pain is one of the most significant chal- last about 15 30 min (Ott, 1994). lenges in the history of medicine. At present, there are still many challenges that hamper pain’s appropriate treatment, as recently stated by American Pain Society (Gereau et al., CASE DESCRIPTION 2014). -
Targeting Nitric Oxide and NMDA Receptor-Associated Pathways in Treatment of High Grade Glial Tumors
Nitric Oxide 79 (2018) 68–83 Contents lists available at ScienceDirect Nitric Oxide journal homepage: www.elsevier.com/locate/yniox Targeting nitric oxide and NMDA receptor-associated pathways in treatment of high grade glial tumors. Hypotheses for nitro-memantine and nitrones T ∗ Meric A. Altinoz , İlhan Elmaci Neuroacademy Group, Department of Neurosurgery, Memorial Hospital, Istanbul, Turkey ARTICLE INFO ABSTRACT Keywords: Glioblastoma multiforme (GBM) is a devastating brain cancer with no curative treatment. Targeting Nitric Oxide Nitric oxide (NO) and glutamatergic pathways may help as adjunctive treatments in GBM. NO at low doses promotes tu- Nitrone morigenesis, while at higher levels (above 300 nM) triggers apoptosis. Gliomas actively secrete high amounts of Nitro-memantine glutamate which activates EGR signaling and mediates degradation of peritumoral tissues via excitotoxic injury. Glial tumor Memantine inhibits NMDA-subtype of glutamate receptors (NMDARs) and induces autophagic death of glioma Glioblastoma cells in vitro and blocks glioma growth in vivo. Nitro-memantines may exert further benefits by limiting NMDAR signaling and by delivery of NO to the areas of excessive NMDAR activity leading NO-accumulation at tumor- icidal levels within gliomas. Due to the duality of NO in tumorigenesis, agents which attenuate NO levels may also act beneficial in treatment of GBM. Nitrone compounds including N-tert-Butyl-α-phenylnitrone (PBN) and its disulfonyl-phenyl derivative, OKN-007 suppress free radical formation in experimental cerebral ischemia. OKN-007 failed to show clinical efficacy in stroke, but trials demonstrated its high biosafety in humans including elderly subjects. PBN inhibits the signaling pathways of NF-κB, inducible nitric oxide synthase (iNOS) and cy- clooxygenase (COX). -
Corymine Potentiates NMDA-Induced Currents in Xenopus Oocytes Expressing Nr1a/NR2B Glutamate Receptors
J Pharmacol Sci 98, 58 – 65 (2005) Journal of Pharmacological Sciences ©2005 The Japanese Pharmacological Society Full Paper Corymine Potentiates NMDA-Induced Currents in Xenopus Oocytes Expressing NR1a/NR2B Glutamate Receptors Pathama Leewanich1,2,*, Michihisa Tohda2, Hiromitsu Takayama3, Samaisukh Sophasan4, Hiroshi Watanabe2, and Kinzo Matsumoto2 1Department of Pharmacology, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand 2Division of Medicinal Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan 3Laboratory of Molecular Structure and Biological Function, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan 4Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand Received January 5, 2005; Accepted March 31, 2005 Abstract. Previous studies demonstrated that corymine, an indole alkaloid isolated from the leaves of Hunter zeylanica, dose-dependently inhibited strychnine-sensitive glycine-induced currents. However, it is unclear whether this alkaloid can modulate the function of the N-methyl- D-aspartate (NMDA) receptor on which glycine acts as a co-agonist via strychnine-insensitive glycine binding sites. This study aimed to evaluate the effects of corymine on NR1a/NR2B NMDA receptors expressed in Xenopus oocytes using the two-electrode voltage clamp technique. Corymine significantly potentitated the NMDA-induced currents recorded from oocytes on days 3 and 4 after cRNA injection but it showed no effect when the current was recorded on days 5 and 6. The potentiating effect of corymine on NMDA-induced currents was induced in the presence of a low concentration of glycine (≤0.1 µM). Spermine significantly enhanced the potentiating effect of corymine observed in the oocytes on days 3 and 4, while the NMDA- receptor antagonist 2-amino-5-phosphonopentanone (AP5) and the NMDA-channel blocker 5- methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) reversed the effect of corymine. -
(200731) Hypromellose Phthalate (220824) Ibudilast
21222122 Infrared Reference Spectra JP XVII Hypromellose Phthalate (200731) Hypromellose Phthalate (220824) Ibudilast The JP Drugs are to be tested according to the provisions given in the pertinent monographs, General Notices, General Rules for Crude Drugs, General Rules for Preparations, and General Tests for their conformity to the Japanese Pharmacopoeia. (See the General Notices 5.) JP XVII Infrared Reference Spectra 21232123 Ibuprofen Ibuprofen Piconol Ifenprodil Tartrate The JP Drugs are to be tested according to the provisions given in the pertinent monographs, General Notices, General Rules for Crude Drugs, General Rules for Preparations, and General Tests for their conformity to the Japanese Pharmacopoeia. (See the General Notices 5.) 21242124 Infrared Reference Spectra JP XVII Imidapril Hydrochloride Imipenem Hydrate Indapamide The JP Drugs are to be tested according to the provisions given in the pertinent monographs, General Notices, General Rules for Crude Drugs, General Rules for Preparations, and General Tests for their conformity to the Japanese Pharmacopoeia. (See the General Notices 5.) JP XVII Infrared Reference Spectra 21252125 Indenolol Hydrochloride Indometacin Iohexol The JP Drugs are to be tested according to the provisions given in the pertinent monographs, General Notices, General Rules for Crude Drugs, General Rules for Preparations, and General Tests for their conformity to the Japanese Pharmacopoeia. (See the General Notices 5.) 21262126 Infrared Reference Spectra JP XVII Iopamidol Iotalamic Acid Iotroxic Acid The JP Drugs are to be tested according to the provisions given in the pertinent monographs, General Notices, General Rules for Crude Drugs, General Rules for Preparations, and General Tests for their conformity to the Japanese Pharmacopoeia. -
MRO Manual Before 2004
Note: This manual is essentially the same as the 1997 HHS Medical Review Officer (MRO) Manual except for changes related to the new Federal Custody and Control Form (CCF). The appendix has also been deleted since the new Federal Custody and Control Form is available as a separate file on the website. Medical Review Officer Manual for Federal Agency Workplace Drug Testing Programs for use with the new Federal Drug Testing Custody and Control Form (OMB Number 0930-0158, Exp Date: June 30, 2003) This manual applies to federal agency drug testing programs that come under Executive Order 12564 and the Department of Health and Human Services (HHS) Mandatory Guidelines. Table of Contents Chapter 1. The Medical Review Officer (MRO) ............................................................... 1 Chapter 2. Federal Drug Testing Custody and Control Form .......................................... 3 Chapter 3. The MRO Review Process ............................................................................ 3 A. Administrative Review of the CCF ........................................................................... 3 I. State Initiatives and Laws ....................................................................................... 15 Chapter 4. Specific Drug Class Issues .......................................................................... 15 A. Amphetamines ....................................................................................................... 15 B. Cocaine ................................................................................................................