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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. -
Designer Drugs SUBJECT FORENSIC SCIENCE
SUBJECT FORENSIC SCIENCE Paper No. and Title PAPER No. 9: Drugs of Abuse Module No. and Title MODULE No. 17: Designer Drugs Module Tag FSC_P9_M17 FORENSIC SCIENCE PAPER No. 9: Drugs of Abuse MODULE No. 17: Designer Drugs TABLE OF CONTENTS 1. Learning Outcomes 2. Introduction 3. Forensic Issues 4. Classification of Designer Drugs 5. Some Notable Designer Drugs 6. Forensic Analysis of Designer Drugs 7. Summary FORENSIC SCIENCE PAPER No. 9: Drugs of Abuse MODULE No. 17: Designer Drugs 1. Learning Outcomes After studying this module, you shall be able to know about: The significance of Designer Drugs Classification of Designer Drugs Forensic analysis of Designer Drugs 2. Introduction Over ages, humans fortunately discovered that certain ingested plants were a source of unique satisfying feelings, beyond satiety. Some were mildly affecting (e.g. nicotine, caffeine), others enhanced mood or altered perception, reduced pain, intoxicated, or produced euphoria (e.g. alcohol, marijuana, hallucinogens, opiates, cocaine). In the past two centuries, consumption of these psychoactive substances expanded rapidly. Decontamination of the active chemicals, distribution by manoeuvres for maximum effect and global marketing contributed to this expansion. Modern chemistry has produced a huge range of variations of these plant products, paralleled by an unprecedented level of adverse biological, behavioural, medical and social consequences. Following this phenomenon, Designer drugs are produced to be similar to, but not identical with Psychoactive Drugs that are illegal to possess or sell for human consumption, unless for medical purposes. A recurring threat to public health, the Designer Drug sub-culture has burst out over the past decade. -
Controlled Substances Included. [M.S.A
1998 PUBLIC AND LOCAL ACTS [No. 319] (HB 4065) AN ACT to amend 1978 PA 368, entitled “An act to protect and promote the public health; to codify, revise, consolidate, classify, and add to the laws relating to public health; to provide for the prevention and control of diseases and disabilities; to provide for the classification, administration, regulation, financing, and maintenance of personal, environ- mental, and other health services and activities; to create or continue, and prescribe the powers and duties of, departments, boards, commissions, councils, committees, task forces, and other agencies; to prescribe the powers and duties of governmental entities and officials; to regulate occupations, facilities, and agencies affecting the public health; to regulate health maintenance organizations and certain third party administrators and insurers; to provide for the imposition of a regulatory fee; to promote the efficient and economical delivery of health care services, to provide for the appropriate utilization of health care facilities and services, and to provide for the closure of hospitals or consolidation of hospitals or services; to provide for the collection and use of data and information; to provide for the transfer of property; to provide certain immunity from liability; to regulate and prohibit the sale and offering for sale of drug paraphernalia under certain circumstances; to provide for penalties and remedies; to provide for sanctions for violations of this act and local ordinances; to repeal certain acts and parts of acts; to repeal certain parts of this act; and to repeal certain parts of this act on specific dates,” by amending sections 7218 and 7401 (MCL 333.7218 and 333.7401), section 7401 as amended by 1996 PA 249, and by adding section 7401a. -
SENATE BILL No. 52
As Amended by Senate Committee Session of 2017 SENATE BILL No. 52 By Committee on Public Health and Welfare 1-20 1 AN ACT concerning the uniform controlled substances act; relating to 2 substances included in schedules I, II and V; amending K.S.A. 2016 3 Supp. 65-4105, 65-4107 and 65-4113 and repealing the existing 4 sections. 5 6 Be it enacted by the Legislature of the State of Kansas: 7 Section 1. K.S.A. 2016 Supp. 65-4105 is hereby amended to read as 8 follows: 65-4105. (a) The controlled substances listed in this section are 9 included in schedule I and the number set forth opposite each drug or 10 substance is the DEA controlled substances code which has been assigned 11 to it. 12 (b) Any of the following opiates, including their isomers, esters, 13 ethers, salts, and salts of isomers, esters and ethers, unless specifically 14 excepted, whenever the existence of these isomers, esters, ethers and salts 15 is possible within the specific chemical designation: 16 (1) Acetyl fentanyl (N-(1-phenethylpiperidin-4-yl)- 17 N-phenylacetamide)......................................................................9821 18 (2) Acetyl-alpha-methylfentanyl (N-[1-(1-methyl-2-phenethyl)-4- 19 piperidinyl]-N-phenylacetamide)..................................................9815 20 (3) Acetylmethadol.............................................................................9601 21 (4) AH-7921 (3.4-dichloro-N-[(1- 22 dimethylaminocyclohexylmethyl]benzamide)...............................9551 23 (4)(5) Allylprodine...........................................................................9602 -
Federal Register/Vol. 85, No. 178/Monday, September 14, 2020
Federal Register / Vol. 85, No. 178 / Monday, September 14, 2020 / Notices 56631 agreements. All non-confidential DEPARTMENT OF JUSTICE ADDRESSES: Written comments should written submissions will be available for be sent to: Drug Enforcement public inspection at the Office of the Drug Enforcement Administration Administration, Attention: DEA Federal Secretary and on EDIS. [Docket No. DEA–713] Register Representative/DPW, 8701 The Commission vote for these Morrissette Drive, Springfield, Virginia 22152. All requests for a hearing must determinations took place on September Importer of Controlled Substances Application: Cerilliant Corporation be sent to: Drug Enforcement 8, 2020. Administration, Attn: Administrator, The authority for the Commission’s AGENCY: Drug Enforcement 8701 Morrissette Drive, Springfield, determination is contained in section Administration, Justice. Virginia 22152. All request for a hearing 337 of the Tariff Act of 1930, as ACTION: Notice of application. should also be sent to: (1) Drug amended (19 U.S.C. 1337), and in Part SUMMARY: Cerilliant Corporation has Enforcement Administration, Attn: 210 of the Commission’s Rules of applied to be registered as an importer Hearing Clerk/OALJ, 8701 Morrissette Practice and Procedure (19 CFR part of basic class(es) of controlled Drive, Springfield, Virginia 22152; and 210). substance(s). Refer to Supplemental (2) Drug Enforcement Administration, Attn: DEA Federal Register By order of the Commission. Information listed below for further Representative/DPW, 8701 Morrissette Issued: September 8, 2020. drug information. DATES: Drive, Springfield, Virginia 22152. Lisa Barton, Registered bulk manufacturers of the affected basic class(es), and SUPPLEMENTARY INFORMATION: In Secretary to the Commission. applicants therefore, may file written accordance with 21 CFR 1301.34(a), this [FR Doc. -
Proposed Regulation of the State Board of Pharmacy
PROPOSED REGULATION OF THE STATE BOARD OF PHARMACY LCB File No. R133-14 Workshop July 24, 2014 NAC 453.540 Schedule IV. (NRS 453.146, 639.070) 1. Schedule IV consists of the drugs and other substances listed in this section, by whatever official, common, usual, chemical or trade name designated. 2. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture or preparation containing any of the following narcotic drugs, including, without limitation, their salts, calculated as the free anhydrous base of alkaloid, is hereby enumerated on schedule IV, in quantities: (a) Not more than 1 milligram of difenoxin and not less than 25 micrograms of atropine sulfate per dosage unit; or (b) Dextropropoxyphene (alpha-(+)-4-dimethylamino-1,2-diphenyl-3-methyl-2-propionoxy- butane). 3. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture or preparation which contains any quantity of the following substances, including, without limitation, their salts, isomers and salts of isomers, is hereby enumerated on schedule IV, whenever the existence of such salts, isomers and salts of isomers is possible within the specific chemical designation: Alprazolam; Barbital; Bromazepam; Butorphanol; Camazepam; Carisoprodol; Chloral betaine; Chloral hydrate; Chlordiazepoxide; Clobazam; Clonazepam; Clorazepate; Clotiazepam; Cloxazolam; Delorazepam; Diazepam; Dichloralphenazone; Estazolam; Ethchlorvynol; Ethyl loflazepate; Fludiazepam; Flunitrazepam; --1-- Agency Draft of Proposed Regulation R133-14 Flurazepam; Halazepam; Haloxazolam; Ketazolam; Loprazolam; Lorazepam; Lormetazepam; Mebutamate; Medazepam; Meprobamate; Methohexital; Methylphenobarbital (mephobarbital); Midazolam; Nimetazepam; Nitrazepam; Nordiazepam; Oxazepam; Oxazolam; Paraldehyde; Petrichloral; Phenobarbital; Pinazepam; Prazepam; Quazepam; Tramadol (2-((dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexanol) Temazepam; Tetrazepam; Triazolam; Zaleplon; Zolpidem; or Zopiclone. -
(12) United States Patent (10) Patent No.: US 8,603,526 B2 Tygesen Et Al
USOO8603526B2 (12) United States Patent (10) Patent No.: US 8,603,526 B2 Tygesen et al. (45) Date of Patent: Dec. 10, 2013 (54) PHARMACEUTICAL COMPOSITIONS 2008. O152595 A1 6/2008 Emigh et al. RESISTANT TO ABUSE 2008. O166407 A1 7/2008 Shalaby et al. 2008/0299.199 A1 12/2008 Bar-Shalom et al. 2008/0311205 A1 12/2008 Habib et al. (75) Inventors: Peter Holm Tygesen, Smoerum (DK); 2009/0022790 A1 1/2009 Flath et al. Jan Martin Oevergaard, Frederikssund 2010/0203129 A1 8/2010 Andersen et al. (DK); Karsten Lindhardt, Haslev (DK); 2010/0204259 A1 8/2010 Tygesen et al. Louise Inoka Lyhne-versen, Gentofte 2010/0239667 A1 9/2010 Hemmingsen et al. (DK); Martin Rex Olsen, Holbaek 2010, O291205 A1 11/2010 Downie et al. (DK); Anne-Mette Haahr, Birkeroed 2011 O159100 A1 6/2011 Andersen et al. (DK); Jacob Aas Hoellund-Jensen, FOREIGN PATENT DOCUMENTS Frederikssund (DK); Pemille Kristine Hoeyrup Hemmingsen, Bagsvaerd DE 20 2006 014131 1, 2007 (DK) EP O435,726 8, 1991 EP O493513 7, 1992 EP O406315 11, 1992 (73) Assignee: Egalet Ltd., London (GB) EP 1213014 6, 2002 WO WO 89,09066 10, 1989 (*) Notice: Subject to any disclaimer, the term of this WO WO91,040 15 4f1991 patent is extended or adjusted under 35 WO WO95/22962 8, 1995 U.S.C. 154(b) by 489 days. WO WO99,51208 10, 1999 WO WOOOf 41704 T 2000 WO WO 03/024426 3, 2003 (21) Appl. No.: 12/701,429 WO WOO3,O24429 3, 2003 WO WOO3,O24430 3, 2003 (22) Filed: Feb. -
Title 16. Crimes and Offenses Chapter 13. Controlled Substances Article 1
TITLE 16. CRIMES AND OFFENSES CHAPTER 13. CONTROLLED SUBSTANCES ARTICLE 1. GENERAL PROVISIONS § 16-13-1. Drug related objects (a) As used in this Code section, the term: (1) "Controlled substance" shall have the same meaning as defined in Article 2 of this chapter, relating to controlled substances. For the purposes of this Code section, the term "controlled substance" shall include marijuana as defined by paragraph (16) of Code Section 16-13-21. (2) "Dangerous drug" shall have the same meaning as defined in Article 3 of this chapter, relating to dangerous drugs. (3) "Drug related object" means any machine, instrument, tool, equipment, contrivance, or device which an average person would reasonably conclude is intended to be used for one or more of the following purposes: (A) To introduce into the human body any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (B) To enhance the effect on the human body of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (C) To conceal any quantity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; or (D) To test the strength, effectiveness, or purity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state. (4) "Knowingly" means having general knowledge that a machine, instrument, tool, item of equipment, contrivance, or device is a drug related object or having reasonable grounds to believe that any such object is or may, to an average person, appear to be a drug related object. -
Proposed Regulation of the State Board of Pharmacy
PROPOSED REGULATION OF THE STATE BOARD OF PHARMACY LCB File No. R150-16 Workshop September 8, 2016 Explanation – Language in blue italics is new; language in red text [omitted material] is language to be omitted, and language in green text indicates prior Board-approved amendments that are in the process of being codified. AUTHORITY: §1, NRS 639.070 A REGULATION relating to controlled substances; adding certain substances to the controlled substances listed in Schedule IV; and providing other matters properly relating thereto. Section 1. NAC 453.540 is hereby amended to read as follows: NAC 453.540 Schedule IV. 1. Schedule IV consists of the drugs and other substances listed in this section, by whatever official, common, usual, chemical or trade name designated. 2. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture or preparation containing any of the following narcotic drugs, including, without limitation, their salts, calculated as the free anhydrous base of alkaloid, is hereby enumerated on schedule IV, in quantities: (a) Not more than 1 milligram of difenoxin and not less than 25 micrograms of atropine sulfate per dosage unit; or (b) Dextropropoxyphene (alpha-(+)-4-dimethylamino-1,2-diphenyl-3-methyl-2-propionoxy- butane). 3. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture or preparation which contains any quantity of the following substances, including, without limitation, their salts, isomers and salts of isomers, is hereby enumerated -
Controlled Substances Included; Rules. Sec. 7216
PUBLIC HEALTH CODE (EXCERPT) Act 368 of 1978 333.7216 Schedule 3; controlled substances included; rules. Sec. 7216. (1) The following controlled substances are included in schedule 3: (a) Unless listed in another schedule, any material, compound, mixture, or preparation containing any quantity of the following substances having a potential for abuse associated with a stimulant effect on the central nervous system, including their salts, isomers, including optical, position, or geometric isomers, and salts of the isomers if the existence of the salts, isomers, and salts of isomers is possible within the specific chemical designation: Benzphetamine Mediatric tabs Chlorphentermine Mediatric liquid Clortermine Phendimetrazine Edrisal tabs Special formula 711 tabs Genegesic caps Thora Dex No. 1 tab Hovizyme tabs Thora Dex No. 2 tab Mazindol (b) Unless listed in another schedule, any material, compound, mixture, or preparation containing any quantity of the following substances having a potential for abuse associated with a depressant effect on the central nervous system, including their salts, isomers, including optical, position, or geometric isomers, and salts of the isomers if the existence of the salts, isomers, and salts of isomers is possible within the specific chemical designation: Chlorhexadol Phencyclidine Glutethimide Sulfondiethylmethane Lysergic acid Sulfonethylmethane Lysergix acid amide Sulfonmethane Methyprylon (c) Nalorphine. (d) Any substance that contains any quantity of a derivative of barbituric acid, or any salt of a derivative of barbituric acid, except those substances that are specifically listed in other schedules. (e) A compound, mixture, or preparation containing amobarbital, secobarbital, pentobarbital, or a salt of amobarbital, secobarbital, or pentobarbital, and 1 or more other active medicinal ingredients that are not listed in a schedule. -
124.210 Schedule IV — Substances Included. 1
1 CONTROLLED SUBSTANCES, §124.210 124.210 Schedule IV — substances included. 1. Schedule IV shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. 2. Narcotic drugs. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation containing any of the following narcotic drugs, or their salts calculated as the free anhydrous base or alkaloid, in limited quantities as set forth below: a. Not more than one milligram of difenoxin and not less than twenty-five micrograms of atropine sulfate per dosage unit. b. Dextropropoxyphene (alpha-(+)-4-dimethylamino-1,2-diphenyl-3-methyl-2- propionoxybutane). c. 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol, its salts, optical and geometric isomers and salts of these isomers (including tramadol). 3. Depressants. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances, including its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation: a. Alprazolam. b. Barbital. c. Bromazepam. d. Camazepam. e. Carisoprodol. f. Chloral betaine. g. Chloral hydrate. h. Chlordiazepoxide. i. Clobazam. j. Clonazepam. k. Clorazepate. l. Clotiazepam. m. Cloxazolam. n. Delorazepam. o. Diazepam. p. Dichloralphenazone. q. Estazolam. r. Ethchlorvynol. s. Ethinamate. t. Ethyl Loflazepate. u. Fludiazepam. v. Flunitrazepam. w. Flurazepam. x. Halazepam. y. Haloxazolam. z. Ketazolam. aa. Loprazolam. ab. Lorazepam. ac. Lormetazepam. ad. Mebutamate. ae. Medazepam. af. Meprobamate. ag. Methohexital. ah. Methylphenobarbital (mephobarbital). -
Revise Schedule of Controlled Substances. (Public) Sponsors: Senators J
GENERAL ASSEMBLY OF NORTH CAROLINA SESSION 2017 S 1 SENATE BILL 347* Short Title: Revise Schedule of Controlled Substances. (Public) Sponsors: Senators J. Davis, McInnis (Primary Sponsors); and Rabin. Referred to: Rules and Operations of the Senate March 22, 2017 1 A BILL TO BE ENTITLED 2 AN ACT REVISING THE SCHEDULE OF CONTROLLED SUBSTANCES TO ADD 3 SYNTHETIC FENTANYLS, DESIGNER HALLUCINOGENICS, SYNTHETIC 4 CANNABINOIDS, SYSTEM DEPRESSANTS, AND OTHER SUBSTANCES. 5 The General Assembly of North Carolina enacts: 6 SECTION 1. This act shall be known and may be cited as the "Synthetic Opioid 7 and Other Dangerous Drug Control Act." 8 SECTION 2. G.S. 90-89 reads as rewritten: 9 "§ 90-89. Schedule I controlled substances. 10 This schedule includes the controlled substances listed or to be listed by whatever official 11 name, common or usual name, chemical name, or trade name designated. In determining that a 12 substance comes within this schedule, the Commission shall find: a high potential for abuse, no 13 currently accepted medical use in the United States, or a lack of accepted safety for use in 14 treatment under medical supervision. The following controlled substances are included in this 15 schedule: 16 (1) Opiates. – Any of the following opiates, including the isomers, esters, ethers, 17 salts and salts of isomers, esters, and ethers, unless specifically excepted, or 18 listed in another schedule, whenever the existence of such isomers, esters, 19 ethers, and salts is possible within the specific chemical designation: 20 a. Acetyl-alpha-methylfentanyl 21 (N[1-(1-methyl-2-phenethyl)-4/y-piperidinyl]-N-phenylacet amide).