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INVESTIGATION of NATURAL PRODUCT SCAFFOLDS for the DEVELOPMENT of OPIOID RECEPTOR LIGANDS by Katherine M
INVESTIGATION OF NATURAL PRODUCT SCAFFOLDS FOR THE DEVELOPMENT OF OPIOID RECEPTOR LIGANDS By Katherine M. Prevatt-Smith Submitted to the graduate degree program in Medicinal Chemistry and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. _________________________________ Chairperson: Dr. Thomas E. Prisinzano _________________________________ Dr. Brian S. J. Blagg _________________________________ Dr. Michael F. Rafferty _________________________________ Dr. Paul R. Hanson _________________________________ Dr. Susan M. Lunte Date Defended: July 18, 2012 The Dissertation Committee for Katherine M. Prevatt-Smith certifies that this is the approved version of the following dissertation: INVESTIGATION OF NATURAL PRODUCT SCAFFOLDS FOR THE DEVELOPMENT OF OPIOID RECEPTOR LIGANDS _________________________________ Chairperson: Dr. Thomas E. Prisinzano Date approved: July 18, 2012 ii ABSTRACT Kappa opioid (KOP) receptors have been suggested as an alternative target to the mu opioid (MOP) receptor for the treatment of pain because KOP activation is associated with fewer negative side-effects (respiratory depression, constipation, tolerance, and dependence). The KOP receptor has also been implicated in several abuse-related effects in the central nervous system (CNS). KOP ligands have been investigated as pharmacotherapies for drug abuse; KOP agonists have been shown to modulate dopamine concentrations in the CNS as well as attenuate the self-administration of cocaine in a variety of species, and KOP antagonists have potential in the treatment of relapse. One drawback of current opioid ligand investigation is that many compounds are based on the morphine scaffold and thus have similar properties, both positive and negative, to the parent molecule. Thus there is increasing need to discover new chemical scaffolds with opioid receptor activity. -
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. -
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Exercise 32 Answers Exercise 32 Answers
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SALVIA DIVINORUM and SALVINORIN a (Street Names: Maria Pastora, Sage of the Seers, Diviner’S Sage, Salvia, Sally-D, Magic Mint) March 2020
Drug Enforcement Administration Diversion Control Division Drug & Chemical Evaluation Section SALVIA DIVINORUM AND SALVINORIN A (Street Names: Maria Pastora, Sage of the Seers, Diviner’s Sage, Salvia, Sally-D, Magic Mint) March 2020 Introduction: from Mexico and Central and South America. The Internet Salvia divinorum is a perennial herb in the mint family is used for the promotion and distribution of Salvia divinorum. native to certain areas of the Sierra Mazateca region of It is sold as seeds, plant cuttings, whole plants, fresh and Oaxaca, Mexico. The plant, which can grow to over three dried leaves, extract-enhanced leaves of various strengths feet in height, has large green leaves, hollow square stems (e.g., 5x, 10x, 20x, 30x), and liquid extracts purported to and white flowers with purple calyces, can also be grown contain salvinorin A. These products are also sold at local successfully outside of this region. Salvia divinorum has shops (e.g., head shops and tobacco shops). been used by the Mazatec Indians for its ritual divination and healing. The active constituent of Salvia divinorum has been User Population: identified as salvinorin A. Currently, neither Salvia divinorum According to the National Survey on Drug Use and nor any of its constituents, including salvinorin A, are Health (NSDUH), published by SAMHSA, it is estimated that controlled under the federal Controlled Substances Act 5.3 million persons, aged 12 or older, used Salvia divinorum (CSA). in their lifetime in 2016 in comparison to 5.1 million persons a year ago in 2015 and 1.8 million persons a decade ago in Licit Uses: 2006. -
Rhyme Rhythm and Repetition Worksheets Rhyme Rhythm and Repetition
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Drugs of Abuseon September Archived 13-10048 No
U.S. DEPARTMENT OF JUSTICE DRUG ENFORCEMENT ADMINISTRATION WWW.DEA.GOV 9, 2014 on September archived 13-10048 No. v. Stewart, in U.S. cited Drugs of2011 Abuse EDITION A DEA RESOURCE GUIDE V. Narcotics WHAT ARE NARCOTICS? Also known as “opioids,” the term "narcotic" comes from the Greek word for “stupor” and originally referred to a variety of substances that dulled the senses and relieved pain. Though some people still refer to all drugs as “narcot- ics,” today “narcotic” refers to opium, opium derivatives, and their semi-synthetic substitutes. A more current term for these drugs, with less uncertainty regarding its meaning, is “opioid.” Examples include the illicit drug heroin and pharmaceutical drugs like OxyContin®, Vicodin®, codeine, morphine, methadone and fentanyl. WHAT IS THEIR ORIGIN? The poppy papaver somniferum is the source for all natural opioids, whereas synthetic opioids are made entirely in a lab and include meperidine, fentanyl, and methadone. Semi-synthetic opioids are synthesized from naturally occurring opium products, such as morphine and codeine, and include heroin, oxycodone, hydrocodone, and hydromorphone. Teens can obtain narcotics from friends, family members, medicine cabinets, pharmacies, nursing 2014 homes, hospitals, hospices, doctors, and the Internet. 9, on September archived 13-10048 No. v. Stewart, in U.S. cited What are common street names? Street names for various narcotics/opioids include: ➔ Hillbilly Heroin, Lean or Purple Drank, OC, Ox, Oxy, Oxycotton, Sippin Syrup What are their forms? Narcotics/opioids come in various forms including: ➔ T ablets, capsules, skin patches, powder, chunks in varying colors (from white to shades of brown and black), liquid form for oral use and injection, syrups, suppositories, lollipops How are they abused? ➔ Narcotics/opioids can be swallowed, smoked, sniffed, or injected. -
Mercury Optimax 225 2011 Engine Cowling Replacement Cost Mercury Optimax 225 2011
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NIDA Drug Supply Program Catalog, 25Th Edition
RESEARCH RESOURCES DRUG SUPPLY PROGRAM CATALOG 25TH EDITION MAY 2016 CHEMISTRY AND PHARMACEUTICS BRANCH DIVISION OF THERAPEUTICS AND MEDICAL CONSEQUENCES NATIONAL INSTITUTE ON DRUG ABUSE NATIONAL INSTITUTES OF HEALTH DEPARTMENT OF HEALTH AND HUMAN SERVICES 6001 EXECUTIVE BOULEVARD ROCKVILLE, MARYLAND 20852 160524 On the cover: CPK rendering of nalfurafine. TABLE OF CONTENTS A. Introduction ................................................................................................1 B. NIDA Drug Supply Program (DSP) Ordering Guidelines ..........................3 C. Drug Request Checklist .............................................................................8 D. Sample DEA Order Form 222 ....................................................................9 E. Supply & Analysis of Standard Solutions of Δ9-THC ..............................10 F. Alternate Sources for Peptides ...............................................................11 G. Instructions for Analytical Services .........................................................12 H. X-Ray Diffraction Analysis of Compounds .............................................13 I. Nicotine Research Cigarettes Drug Supply Program .............................16 J. Ordering Guidelines for Nicotine Research Cigarettes (NRCs)..............18 K. Ordering Guidelines for Marijuana and Marijuana Cigarettes ................21 L. Important Addresses, Telephone & Fax Numbers ..................................24 M. Available Drugs, Compounds, and Dosage Forms ..............................25 -
WO 2017/066488 Al
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date W O 2017/066488 A l 2 0 April 2017 (20.04.2017) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 31/485 (2006.01) A61P 25/04 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/5415 (2006.01) A61P 1/08 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, (21) International Application Number: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US20 16/0569 10 HN, HR, HU, ID, IL, EST, IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, 13 October 2016 (13.10.201 6) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (25) Filing Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (26) Publication Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 62/240,965 13 October 2015 (13. 10.2015) US (84) Designated States (unless otherwise indicated, for every 62/300,014 25 February 2016 (25.02.2016) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (71) Applicant: CHARLESTON LABORATORIES, INC. -
Exploring Hallucinogen Pharmacology and Psychedelic Medicine with Zebrafish Models
ZEBRAFISH Volume 13, Number 5, 2016 Review Articles ª Mary Ann Liebert, Inc. DOI: 10.1089/zeb.2016.1251 Exploring Hallucinogen Pharmacology and Psychedelic Medicine with Zebrafish Models Evan J. Kyzar1 and Allan V. Kalueff2–6 Abstract After decades of sociopolitical obstacles, the field of psychiatry is experiencing a revived interest in the use of hallucinogenic agents to treat brain disorders. Along with the use of ketamine for depression, recent pilot studies have highlighted the efficacy of classic serotonergic hallucinogens, such as lysergic acid diethylamide and psilocybin, in treating addiction, post-traumatic stress disorder, and anxiety. However, many basic phar- macological and toxicological questions remain unanswered with regard to these compounds. In this study, we discuss psychedelic medicine as well as the behavioral and toxicological effects of hallucinogenic drugs in zebrafish. We emphasize this aquatic organism as a model ideally suited to assess both the potential toxic and therapeutic effects of major known classes of hallucinogenic compounds. In addition, novel drugs with hal- lucinogenic properties can be efficiently screened using zebrafish models. Well-designed preclinical studies utilizing zebrafish can contribute to the reemerging treatment paradigm of psychedelic medicine, leading to new avenues of clinical exploration for psychiatric disorders. Introduction requiring the use of both traditional (rodent) and novel model species.6 In this study, we briefly review the history of psy- allucinogenic drugs have been used by humans for chedelic medicine and the pharmacology of these drugs and centuries, exerting potent effects on thought, cognition, H discuss the effects of hallucinogenic drugs on larval and adult and behavior with little propensity for habit formation and zebrafish (Danio rerio). -
ERMA200009 Salvia Decision Vfinal
DETERMINATION ON WHETHER A SUBSTANCE IS A HAZARDOUS SUBSTANCE PURSUANT TO SECTION 26 OF THE HSNO ACT 29 October 2009 Application Code ERMA200009 Application Type To determine whether a substance is hazardous under Section 26 of the Hazardous Substances and New Organisms Act 1996 (“the Act”). Applicant Ministry of Health Date Application Received 24 July 2009 Consideration Date 29 October 2009 Considered by A Committee of the Authority (“the Committee”) Purpose of the Application To determine whether preparations of Salvia Divinorum are hazardous. 1 Application process 1.1 The Agency received an application requesting a formal determination on whether preparations of Salvia Divinorum are hazardous substances under section 26 of the HSNO Act. 1.2 The application was formally received on 24 July 2009. 1.3 The evaluation of the application was undertaken by the ERMA New Zealand project team (“the Agency”) which comprised the following staff members: Matthew Allen Advisor (Hazardous Substances) Tonderai Kaitano Advisor (Hazardous Substances) 1.4 The report was reviewed and signed out by: Lynne Waterson Applications Manager (Hazardous Substances). 1.5 No external experts were used in the consideration of this application. 1.6 The following members of the Authority considered the application: Helen Atkins (Chair) and Shaun Ogilvie. 1.7 The information available to the Committee comprised: the application; and this report. 2 Background to the application Purpose of the application 2.1 To determine whether preparations of Salvia Divinorum (i.e. preparations of Salvia Divinorum that contain the substance salvinorin-A) are hazardous. Identification of Salvinorin-A 2.2 Salvia Divinorum is a perennial herb of the mint family native to Mexico which is now also grown in many countries (Drug Enforcement Administration, 2008).