DOCSLIB.ORG

Gamma-Hydroxybutyrate (GHB) and Its Derivatives: a New and Novel Neuroactive Drug of Abuse

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Gamma-Hydroxybutyrate (GHB) and Its Derivatives: a New and Novel Neuroactive Drug of Abuse Chula Mad J Vol. 48 No.7 July 2004 Gamma-Hydroxybutyrate (GHB) and its derivatives: A new and novel neuroactive drug of abuse Krisda Sirampuj* Sirampuj K. Gamma-Hydroxybutyrate (GHB) and its derivatives: A new and novel neuroactive drug of abuse. Chula Med J 2004 Jul; 48(7): 491 - 502 There has been increasing attention in the abuse of gamma-hydroxybutyrate (GHB) , with some evidence in other parts of the world especially the United States. In vitro and animal research models show that, while GHB shares certain properties with some depressant drugs abusive to central nervous system, it also has unique aspects of its pharmacology including actions at a specific neural receptor which probably mediates many of its effects. So far, the assessment of the abusive potential of GHB with standard animal models has not yielded a picture of a highly abusive substance, and little testing of the drug in human has been done. Vel}' little systematic data exist on the tolerance and dependence of GHB, but both have been seen in human users. Quantitative data on the prevalence of GHB abuse is incomplete, but various qualitative measures indicate that a mini-epidemic of GHB abuse began in the late 1980s and continues to the present. GHB is often included with the group of the so-called 'club drugs', which can be used as an intoxicant. It also has been used as a growth promoter and sleep-aid agent, also implicated in cases of 'date rape', usually in combination with alcohol. Undoubtedly the easy availability of GHB and some of its precursors has contributed to its popularity. With as yet unknown consequences for the scope of the public health problem, recent changes in the control status of GHB in the US may reduce its availability. Experts on drug abuse need to familiarize themselves with GHB since it has a potentiality to be a new type of problem of drug abuse with some unique properties. Keywords: Gamma-hydroxybutyrate, GHB, Gamma-butyrolactone, GBL, Novel neuroactive drug, New type of drug abuse. Reprint request: Sirampuj K. Faculty of Liberal Arts, Thammasat University, Khong Luang, Prathum Thani 12121, Thailand. E-mail: [email protected] Received for publication: May 15, 2004. Objective: This review highlights the biochemistry, neuropharmacology, and toxicology of the naturally­ occurring fatty acid derivative, gamma-hydroxybutyrate (GHB). GHB is derived from gamma­ aminobutyric acid (GABA) and is proposed to function as an inhibitory chemical transmitter in the central nervous system. The purposes ofthis review also focus on the social effect of this substance and urge the public to aware of its increasing abuse potential. • Faculty of Liberal Arts, Thammasat University 492 Chula Med J n"IV"1 fi"i1 a.I"1tf. un a.I a.l11U""ifl nfJih 1 'VI L"i'VI LUU~fl~\iU 6' if1"ifl fl n"I 'VI BPi flij"t1"i~if1'V1 s11 'l'HaJ;iemha.l1'lllu'VI1,,;iel6l. ~\11ft"n"ialL 1tfif1"i 2547 n.Ft; 4S( 7): 491 - 502 Luiflil~ uuiJ n lr LUf"l,]IU~U Liii LU dfN'!JfJ-Jmr HEJl'll~fJ~ lrdfJfJn q'VIfPifJ'iPllh::~ 1 'VI LU'VJ1-J dCJ(i1Uln~U ~ lrLLnUUl LeJ(i1rfJn~fj'] L'VJLmviffi GHB dju~lrfJfJn q'VIfPl'fJ'iPll1r::~ 1 'VI df"l'fJ U;[I-J L'VI:J P7,]'VId-Jdril;-Jdjuifty'VI1~IFity'VJ1-J~lfjln1J~'!J GHB fJfJnq'VIfPifJP7']flJdr./I'rn::'!JfJ-Jr::lJlJl1r::~I'V1 fI']un~l-J ~-JrifJ LU"7(i1t:J~PifJ~UfJ-JLU'VI~IEJ~IU iJmr~n'1Yln-Jt:J~'~EJ'!JfJ-J GHB fJcJl-JUln LuiPl{ 'VI(i1 ~fJ.J LLPI'n 6-J L:JL~IlIWdi(i1' IiIUfJfJ nUl fI ']u LUU'lf'1Y66-JiJ n lr~n '1Y1UfJ EJUI n iJLLPi;[fJ3J~ "rEJ']t7lJ nlrfJfJnq'VIfLu~lunlmuPifJq'VIfEJ1LL~::nlr'~W~(i1 ;[fJ3J~ LU~lulEUlru'!JfJ-Jf"l,]IU1nmrH~lr GHB LL~::fJ'lfWUfj1U'VJ1-JdL:JL'V/Ul::~u6-JL:JiJ ,.... '1,1 P1,]'~'!J)?i(i1'IiIU LLPI'liIlnmr:;i(i1'V11-J~IUFJrulllWWlJlhiJmrUilu'VI1-J)?CJ(i1fJcJl-JLLWi'VI~IEJP7-JLLPi"ll,]-J l1~IEJ'VIMrr'1Y 1980 liIun-Jiflil~uu ~lr GHB 3J'nQnL-rlu'VI3J";mdmn~I-J~UliluiJ~fJLrEJn11 'EJld L-rlUf"l;lJ' UfJnlillna GHB 6-JQn'-%dju~lrL'~ungfl,i!fJLL~::mr'liI~ty'~lJLPlLurJLW1::mEJLL~::H ,iJUEJ1UfJU 'VI;lJ LurJd iJ ifty'VIl n1 rUfJ U LUlJl-Jf"l n'] Hi']u t711fr~ nfJ eJf1ffi ~fJ m r~'fJ ~,]-J'VI l-J' WPI " J,I .., , ,ilfJ-J1iI In)? ehUUl n lr'VI1~fJ~ lr GHB LL~::~ 1 rP7-Jtlru)?L-rlumrt:JflPlf"l'fJU;[I-J,h EJ~-Jnl LUiJlEUI ru , , ., mrL-%)?~-J "PI'Luiflil~UU LU~'VIf.!fJ,u~m L~iJmr,l1ftEJumJ~-J L(i1EJril'V1U(i1 LU GHB "~::~lrP7-Jtlru ,iJu~lrdfJ~LUnfJ'Uf"l,]lJFJUUln~U '~fJiJfJ-Jt7Uifty'VI1'V11-J~lfjlrru~'!Jdd7(i11i11nmrL-%EJ1CJ(i1iPlfJ l1r::~-Jrr ..., , , U'VI f"l,]IUi1iJ~ (i1l1r::~ -J mWfJ LulJ f"l ~ 1 m'VJ1-J~ lfjlrru~'!J, rJiJfllUlli1)? Lf7 m;[fJ-J Lum rf"l,]u FJU , , 'I" '1 .col... • I It .,..,., .., - .col nlr &'lfEJI &U'VJ1-J'VIt:J(i1, "~::ur::'lfl'lfU &(i1P1r::'VIun"~::'VInu'!JfJ3J~'!JfJ-J~lr GHB "~::fJ'lfWUfj'11-JU "U'] Luudlil::iJ m r L-rl U'VI l-Jd, 'VIU1::~ u "~::fJlli1 LiJU~ 1 rL~ W~ WJ1iJ(i1 L'VI:Jd':h 1l1~ifty'VI1'V1 l-Ji-Jf"lU LL~::~lfjlrru~'!J Pi1Ihfi'Y: LLnUUl LeJ(i1rfJn~fj'] L'VIL~PI, "nUU1U'] 1'VI L~"~n LPlU, EJlfJfJnq'VIfPifJ~Pll1~::~I'V1P7,] L'VI:J, EJldL-rlunl~~'fJ~,]-J'VI1-JLWPI Vol. 48 No.7 493 July 2004 Gamma-Hydroxybutyrate (GHB; 4-hydro­ its hypnotic effects and its ability to incapacitate xybutyrate, 4-hydroxybutyric acid) is a central victims (mostly women) for purposes of sexual neuromodulator synthesized locally from Gamma­ assault. GHB produces a state of relaxation and aminobutyric acid(GABA) which is an endogenous tranquility accompanied by feelings of calmness, mild constituent of mammalian brains. Synthetic GHB was euphoria. As the dose of these drugs is increased, a initially developed as anesthetic agents and was sold sharp increase in adverse effects may occur. in the US in health food store as a performance Overdoses with these drugs can result in life­ enhancing additive in bodybuilding formulas. However threatening symptoms of CNS depression, coma, in 1990, the US Food and Drug administration (FDA) respiratory depression, apnea, bradycardia, banned its distribution due to its widespread reports hypotension, and seizures.(3) According to the Drug of poisoning and adverse reactions. In 2000, GHB Abuse Warning Network (DAWN), GHB emergency was placed into schedule I of the Federal Controlled department mentions have increased from 56 in 1994 Substance Act.(1) to 3,340 in 2001. Since 1990, the US Drug Enforcement Administration (DEA) has documented more than Abusive use of GHB 15,600 overdoses and law enforcement encounters Despite being banned by the FDA, GHB is and 72 deaths related to GHB. The FDA has released still widely available in the underground drug market. reports and warning conveying the adverse health There are analogs of GHB; Gammabutyrolactone consequences of GHB, GBL, and 1,4-butanediol. (GBL) and 1,4-butanediol which are marketed as Ingestion of the products containing these substances dietary supplements in health food stores, sport have been linked to at least 122 serious illnesses and nutrition stores and on the internet. GBL is converted three deaths. (2) The FDA has issued warnings for both into GHB in an alkaline environment such as in the GBL and 1,4-butanediol, stating that the drugs presence of sodium or potassium hydroxide and the have a potential for abuse and are a public health reaction is complete in under an hour. Additionally, danger.(1) once digested these analogs of GHB are rapidly metabolized to GHB in vivo by a rapidly acting Situation in Thailand lactonase found in the blood and liver. 1,4-butanediol In 2003, the Food and Drug Administration of is converted to GHB by alcohol dehydrogenase and Thailand reported death of a woman and seven cases aldehyde dehydrogenase. Due to the efficient of serious illness resulted from drinking wine that conversion of both GBL and 1,4-butanediol, their contains GBL, tetrahydrofuran (THF), and acetonitrile toxicological profiles are essentially analogous to that or methyl cyanide.(4.5) The wine was in a lot of 144 of GHB.(2) bottles which two foreigners had been hired to mail Factors that seem to contribute to the the bottles to the US but the company was unable to addictive potential of GHB and its metabolic send it. (4) precursors include its purported anabolic effects, 494 Chula Med J Biotransformation of GHB and THF effects such as behavioral sedation and narcosis in Comparing the structures of GBL with 1, mammals, gastrointestinal tract like nausea, vomiting 4-butanediol and THF, itwas found that each of these and diarrhea and may cause respiratory depression, compounds share the same 4-carbon backbone and coma, and death. Overdose of GHB can cause life­ the differences between them are due to the different threatening effects similar to acute THF toxicity, such functional groups at the C-1 and C-4. Hydrolysis of as respiratory depression, apnea, hypotension, coma GBL opens the 5-membered ring of the 4-carbon and death. Currently there are no antidotes to treat backbone, forming GHB. Conversions of these GHB overdose or THF toxicity. Knowledge about the structure are as follows: the conversion of 1, biotransformation of THF to GHB could be useful in 4-butanediol to THF can be accomplished by designing pharmacological interventions.
Load more

Recommended publications
  • ANNNNNNNNNNNNNNNNNNNN 100A 006 Left Eye Input Right Eye Input
    US 20190175049A1 ( 19) United States (12 ) Patent Application Publication (10 ) Pub. No. : US 2019 /0175049 A1 Welling ( 43 ) Pub . Date : Jun . 13 , 2019 ( 54 ) TECHNIQUES FOR ANALYZING (52 ) U . S . CI. NON -VERBAL MARKERS OF CONDITIONS CPC . .. A61B 5 /04842 (2013 . 01 ) ; A61B 5 / 7289 USING ELECTROPHYSIOLOGICAL DATA (2013 . 01) ; A61B 5 /0478 ( 2013 .01 ) ; A61B 5 /7225 ( 2013. 01 ) ; G06N 20 / 10 (2019 .01 ) (71 ) Applicant: Massachusetts Institute of Technology , Cambridge , MA (US ) ( 57 ) ABSTRACT (72 ) Inventor : Caroline Welling, Hanover, NH (US ) Embodiments related to analyzing brain activity of a subject to identify signs associated with binocular rivalry . Sensed ( 21 ) Appl. No. : 16 / 206, 639 electrical activity of a subject' s brain is received over a time period while the subject is exposed to a visual stimulus. The ( 22 ) Filed : Nov. 30 , 2018 sensed electrical activity comprises a first frequency band Related U . S . Application Data associated with a first frequency of a first image presented to the subject ' s left eye , a second frequency band associated (60 ) Provisional application No .62 / 593 , 535, filed on Dec . with a second frequency of a second image presented to the 1 , 2017 subject ' s right eye . A set of events in the time period is determined based on the frequency bands, wherein an event Publication Classification is associated with a change from a previous perceptual event (51 ) Int. Ci. to a new perceptual event. A metric for the subject is A61B 5 /0484 ( 2006 .01 ) determined based on the set of events . The metric is ana A61B 5 /00 ( 2006 .01 ) lyzed to determine whether the subject exhibits signs asso GO6N 20 / 10 (2006 .01 ) ciated with a condition that is associated with binocular A61B 5 /0478 ( 2006 .01 ) rivalry .
    [Show full text]
  • 194 Recent Advances in the Synthesis of New Pyrazole Derivatives
    194 RECENT ADVANCES IN THE SYNTHESIS OF NEW PYRAZOLE DERIVATIVES DOI: http://dx.medra.org/ 10.17374/targets.2019.22.194 Juan - Carlos Castillo a,b , Jaime Portilla a * a Bioorganic Compounds Research Group, Department of Chemistry, Universi dad de los Andes, Carrera 1 No. 18A - 10, Bogotá, Colombia b Grupo de Cat álisis, E scuela de Ciencias Químicas, Universidad Pedagógica y Tecnológica de Colombia UPTC, Av enida Central del Norte, Tunja, Colombia (e - mail : [email protected] ) Abstract. Pyrazoles have attracted great attention in organic and medicinal chemistry, due to their proven utility as synthetic intermediates for the preparation of diverse bioactive compounds, of coordination complexes, as well as in the design of functional materials. Consequently , the synthesis of functionalized pyrazoles is an important focus of research for synthetic organic chemists. Likewise, fuse d pyrazoles such as pyrazolo[1,5 - a]pyrimidines and pyrazolo[3,4 - b]pyridines have been widely studied due to their varied biological and physicochemical applications based on the important electronic properties of th ese N - heterocycles. Therefore, the preparation of these fused heterocycles and of their functionalized derivatives is of notable interest to both uncover novel derivatives and explore new applications. Several methods have been described in the literature for the synthesis of pyrazoles and of their fused systems in recent years , which mainly involve classi cal cyclocondensation reactions , some of these are presented in th is contribution. Contents 1. Introduction 2. Functionalized pyrazoles 2.1. Aminopyrazoles 2.2. Formylpyrazoles 3. Fused pyrazoles 3.1. Pyrazolo[1,5 - a ]pyrimidines 3.2. Pyrazolo[3,4 - b ]pyridines 3.3.
    [Show full text]
  • Aniline and Aniline Hydrochloride
    SOME AROMATIC AMINES AND RELATED COMPOUNDS VOLUME 127 This publication represents the views and expert opinions of an IARC Working Group on the Identification of Carcinogenic Hazards to Humans, which met remotely, 25 May–12 June 2020 LYON, FRANCE - 2021 IARC MONOGRAPHS ON THE IDENTIFICATION OF CARCINOGENIC HAZARDS TO HUMANS ANILINE AND ANILINE HYDROCHLORIDE 1. Exposure Characterization 1.1.2 Structural and molecular formulae, and relative molecular mass 1.1 Identification of the agent (a) Aniline 1.1.1 Nomenclature NH2 (a) Aniline Chem. Abstr. Serv. Reg. No.: 62-53-3 EC No.: 200-539-3 Molecular formula: C H N IUPAC systematic name: aniline 6 7 Relative molecular mass: 93.13 (NCBI, 2020a). Synonyms and abbreviations: benzenamine; phenylamine; aminobenzene; aminophen; (b) Aniline hydrochloride aniline oil. NH2 (b) Aniline hydrochloride Chem. Abstr. Serv. Reg. No.: 142-04-1 EC No.: 205-519-8 HCl IUPAC systematic name: aniline hydro - Molecular formula: C6H8ClN chloride Relative molecular mass: 129.59 (NCBI, Synonyms: aniline chloride; anilinium chlo- 2020b). ride; benzenamine hydrochloride; aniline. HCl; phenylamine hydrochloride; phenylam- monium chloride. 1.1.3 Chemical and physical properties of the pure substance Aniline is a basic compound and will undergo acid–base reactions. Aniline and its hydrochlo- ride salt will achieve a pH-dependent acid–base equilibrium in the body. 109 IARC MONOGRAPHS – 127 (a) Aniline Octanol/water partition coefficient (P): log Kow, 0.936, predicted median (US EPA, 2020b) Description: aniline appears as a yellowish Conversion factor: 1 ppm = 5.3 mg/m3 [calcu- to brownish oily liquid with a musty fishy lated from: mg/m3 = (relative molecular odour (NCBI, 2020a), detectable at 1 ppm 3 mass/24.45) × ppm, assuming temperature [3.81 mg/m ] (European Commission, 2016; (25 °C) and pressure (101 kPa)].
    [Show full text]
  • Synthetic Turf Scientific Advisory Panel Meeting Materials
    California Environmental Protection Agency Office of Environmental Health Hazard Assessment Synthetic Turf Study Synthetic Turf Scientific Advisory Panel Meeting May 31, 2019 MEETING MATERIALS THIS PAGE LEFT BLANK INTENTIONALLY Office of Environmental Health Hazard Assessment California Environmental Protection Agency Agenda Synthetic Turf Scientific Advisory Panel Meeting May 31, 2019, 9:30 a.m. – 4:00 p.m. 1001 I Street, CalEPA Headquarters Building, Sacramento Byron Sher Auditorium The agenda for this meeting is given below. The order of items on the agenda is provided for general reference only. The order in which items are taken up by the Panel is subject to change. 1. Welcome and Opening Remarks 2. Synthetic Turf and Playground Studies Overview 4. Synthetic Turf Field Exposure Model Exposure Equations Exposure Parameters 3. Non-Targeted Chemical Analysis Volatile Organics on Synthetic Turf Fields Non-Polar Organics Constituents in Crumb Rubber Polar Organic Constituents in Crumb Rubber 5. Public Comments: For members of the public attending in-person: Comments will be limited to three minutes per commenter. For members of the public attending via the internet: Comments may be sent via email to [email protected]. Email comments will be read aloud, up to three minutes each, by staff of OEHHA during the public comment period, as time allows. 6. Further Panel Discussion and Closing Remarks 7. Wrap Up and Adjournment Agenda Synthetic Turf Advisory Panel Meeting May 31, 2019 THIS PAGE LEFT BLANK INTENTIONALLY Office of Environmental Health Hazard Assessment California Environmental Protection Agency DRAFT for Discussion at May 2019 SAP Meeting. Table of Contents Synthetic Turf and Playground Studies Overview May 2019 Update .....
    [Show full text]
  • Synthesis of Pyrazoles Containing Benzofuran and Trifluoromethyl Moieties As Possible Anti-Inflammatory and Analgesic Agents
    Z. Naturforsch. 2015; 70(7)b: 519–526 Awatef A. Farag, Mohamed F. El Shehry, Samir Y. Abbas*, Safaa N. Abd-Alrahman, Abeer A. Atrees, Hiaat Z. Al-basheer and Yousry A. Ammar Synthesis of pyrazoles containing benzofuran and trifluoromethyl moieties as possible anti-inflammatory and analgesic agents DOI 10.1515/znb-2015-0009 and anti-inflammatory drugs present a wide range of prob- Received January 9, 2015; accepted February 4, 2015 lems such as efficacy and undesired effects including gas- trointestinal tract (GIT) disorders and other unwanted effects. This situation highlights the need for novel, safe and Abstract: Searching for new anti-inflammatory and anal- effective analgesic and anti-inflammatory compounds [1–3]. gesic agents, we have prepared a series of novel pyrazoles Since the first pyrazolin-5-one was prepared by Knorr containing benzofuran and trifluoromethyl moieties. The [4] in 1883, many papers have reported on the anti-inflam- pyrazole derivatives have been synthesized via two routes matory, analgesic and antipyretic evaluation of several starting from 5-(3-(trifluoromethyl)phenyl azo) salicylal- pyrazoles, pyrazolin-3-ones and pyrazolidine-3,5-diones dehyde. The first route involved the synthesis of 2-acetylb- [5–9]. Many of these derivatives such as phenylbutazone, enzofuran and then treatment with aldehydes to afford febrazone, feclobuzone, mefobutazone, suxibuzone and the corresponding chalcones. The cyclization of the latter ramifenazone have found their clinical application as chalcones with hydrazine hydrate led to the formation of nonsteroidal anti-inflammatory drugs (NSAIDs) [10]. new pyrazoline derivatives. The second route involved the The benzofuran derivatives have attracted due to their synthesis of benzofuran-2-carbohydrazide and then treat- biological activities and potential application as pharma- ment with formylpyrazoles, chalcones and ketene dith- cological agents [11].
    [Show full text]
  • Introduced B.,Byhansen, 16
    LB301 LB301 2021 2021 LEGISLATURE OF NEBRASKA ONE HUNDRED SEVENTH LEGISLATURE FIRST SESSION LEGISLATIVE BILL 301 Introduced by Hansen, B., 16. Read first time January 12, 2021 Committee: Judiciary 1 A BILL FOR AN ACT relating to the Uniform Controlled Substances Act; to 2 amend sections 28-401, 28-405, and 28-416, Revised Statutes 3 Cumulative Supplement, 2020; to redefine terms; to change drug 4 schedules and adopt federal drug provisions; to change a penalty 5 provision; and to repeal the original sections. 6 Be it enacted by the people of the State of Nebraska, -1- LB301 LB301 2021 2021 1 Section 1. Section 28-401, Revised Statutes Cumulative Supplement, 2 2020, is amended to read: 3 28-401 As used in the Uniform Controlled Substances Act, unless the 4 context otherwise requires: 5 (1) Administer means to directly apply a controlled substance by 6 injection, inhalation, ingestion, or any other means to the body of a 7 patient or research subject; 8 (2) Agent means an authorized person who acts on behalf of or at the 9 direction of another person but does not include a common or contract 10 carrier, public warehouse keeper, or employee of a carrier or warehouse 11 keeper; 12 (3) Administration means the Drug Enforcement Administration of the 13 United States Department of Justice; 14 (4) Controlled substance means a drug, biological, substance, or 15 immediate precursor in Schedules I through V of section 28-405. 16 Controlled substance does not include distilled spirits, wine, malt 17 beverages, tobacco, hemp, or any nonnarcotic substance if such substance 18 may, under the Federal Food, Drug, and Cosmetic Act, 21 U.S.C.
    [Show full text]
  • EFFECTS of CHRONIC and ACUTE Y-HYDROXYBUTYRATE ADMINISTRATION on MASS and the RELEASE of GROWTH HORMONE and CORTICOSTERONE
    EFFECTS OF CHRONIC AND ACUTE y-HYDROXYBUTYRATE ADMINISTRATION ON MASS AND THE RELEASE OF GROWTH HORMONE AND CORTICOSTERONE A Thesis Presented to the Faculty of the College of Science and Technology Morehead State University In Partial Fulfillment of the Requirements for the Degree Master of Science in Biology by Eric C. Goshorn October, 1998 /-t?p-1\'/ I"\s 4 ,he-a ·1 ~ ~lC\ .9~ G ls> 1 lo .JL. Accepted by the faculty of the College of Science and Technology, Morehead State University, in partial fulfillment of the requirements for the Master of Science degree. Master's Committee: /2..-lo -</'?, Date ii EFFECTS OF CHRONIC AND ACUTE y-HYDROXYBUTYRATE ADMINISTRATION ON MASS AND THE RELEASE OF GROWTH HORMONE AND CORTICOSTERONE Eric Christopher Goshorn, M.S. Morehead State University, 1998 Director of Thesis· Gamma-hydroxybutyrate (GHB) is a naturally occurring compound found both in neural (Roth and Suhr 1970) and extraneural tissue (Nelson et al. 1981 ). While the endogenous function of peripheral GHB has yet to be elucidated, experimentation has found that this compound induces anesthesia, and the release of growth hormone and prolactin from the anterior pituitary (Oyama and Takiguchi 1970; Takahara et al. 1977). This study was undertaken to determine the effect of chronic GHB injections on the weight gain of rats during early postnatal development. Acute injections were also administered to rats not previously treated with exogenous GHB to iii ascertain the mechanism of growth hormone release and to determine GHB's effect on corticosterone release. At the age of 3 days, both male and female rats from the chronic group were injected intraperitoneally with 100 mg/kg, 500 mg/kg, or 0 mg/kg of GHB.
    [Show full text]
  • Muscimol-Scopolamine Interactions in the Rat Brain: a Study with 2-Deoxy-D-[ 1-14C]Glucose1
    0270.6474/84/0406-1405$02.00/O The Journal of Neuroscience Copyright 0 Society for Neuroscience Vol. 4, No. 6, pp. 1405-1413 Printed in U.S.A. June 1984 MUSCIMOL-SCOPOLAMINE INTERACTIONS IN THE RAT BRAIN: A STUDY WITH 2-DEOXY-D-[ 1-14C]GLUCOSE1 PAUL1 HELEN AND EDYTHE D. LONDON*x2 Laboratory of Neurosciences, National Institute on Aging, Gerontology Research Center, Baltimore City Hospitals, Baltimore, Maryland 21224 and *National Institute on Drug Abuse, Addiction Research Center, c/o Baltimore City Hospitals, Baltimore, Maryland 21224 Received August 22, 1983; Revised November 29, 1983; Accepted December 6, 1983 Abstract The 2-deoxy-D[1-‘4C]glucose method of Sokoloff was used to measure local cerebral glucose utilization (LCGU) in rats after injections of the GABA receptor agonist, muscimol (1.6 mg/kg and 4.0 mg/kg, i.v.); the muscarinic receptor antagonist, scopolamine (0.4 mg/kg and 2.0 mg/kg, i.v.); or combinations of both drugs. The aim was to identify brain regions where functional effects of GABAergic-cholinergic interactions could be seen. As noted previously, muscimol reduced LCGU in many brain regions. In contrast, scopolamine alone had no effect on LCGU in most brain regions; however, decreases were seen in the medial geniculate body, medial thalamic nucleus, and auditory and frontal cortical areas. Scopolamine increased LCGU in the cerebellar vermis and mesencephalic reticular formation. Although muscimol alone did not significantly affect LCGU in the external plexiform layer of the olfactory bulb or the anterior, periventricular, and parafascicular thalamic nuclei, rats treated with 0.4 mg/kg of scopolamine before 4.0 mg/kg of muscimol had LCGU decrements in those brain regions.
    [Show full text]
  • Heterocyclic Chemistrychemistry
    HeterocyclicHeterocyclic ChemistryChemistry Professor J. Stephen Clark Room C4-04 Email: [email protected] 2011 –2012 1 http://www.chem.gla.ac.uk/staff/stephenc/UndergraduateTeaching.html Recommended Reading • Heterocyclic Chemistry – J. A. Joule, K. Mills and G. F. Smith • Heterocyclic Chemistry (Oxford Primer Series) – T. Gilchrist • Aromatic Heterocyclic Chemistry – D. T. Davies 2 Course Summary Introduction • Definition of terms and classification of heterocycles • Functional group chemistry: imines, enamines, acetals, enols, and sulfur-containing groups Intermediates used for the construction of aromatic heterocycles • Synthesis of aromatic heterocycles • Carbon–heteroatom bond formation and choice of oxidation state • Examples of commonly used strategies for heterocycle synthesis Pyridines • General properties, electronic structure • Synthesis of pyridines • Electrophilic substitution of pyridines • Nucleophilic substitution of pyridines • Metallation of pyridines Pyridine derivatives • Structure and reactivity of oxy-pyridines, alkyl pyridines, pyridinium salts, and pyridine N-oxides Quinolines and isoquinolines • General properties and reactivity compared to pyridine • Electrophilic and nucleophilic substitution quinolines and isoquinolines 3 • General methods used for the synthesis of quinolines and isoquinolines Course Summary (cont) Five-membered aromatic heterocycles • General properties, structure and reactivity of pyrroles, furans and thiophenes • Methods and strategies for the synthesis of five-membered heteroaromatics
    [Show full text]
  • Proceedings of the Indiana Academy of Science
    Michael Addition and Derivatives of 2-Carboxamido-3-phenylindenone' E. Campaigne and David A. Templer Department of Chemistry Indiana University, Bloomington, Indiana 47405 Introduction Recently we have submitted several reports (6,7,8) dealing with the synthesis and reactions of 3-substituted 2-carboxamidoindenones. Among the reactions which these compounds undergo is a fascile Michael addition, and we wish to report here the addi- tion of a variety of nucleophiles to 2-carboxamido-3-phenylindenone (1) and some of the products derived from these compounds. The Michael reaction, now one hundred years old, is a useful synthetic tool that has led to a vast amount of research on its scope and limitations. It is the subject of an extensive review (1). The reaction generally refers to the addition of a nucleophile to a conjugated double bond which involves a series of reversible equilibrium reactions. Thus the reverse of Michael addition may occur, and products may be unstable on isolation. The synthesis of indenones via the cyclization of ylidenemalononitriles has been extensively studied in our laboratories (5). The first reported Michael addition to an in- denone was rather recent. In 1960, Koelsch (9) found that 2-carbethoxy-3-phenyl-l- indenone reacts readily with a variety of carbanions and other nucleophiles to give Michael adducts, but he was unable to alkylate the intermediate ions formed by these reactions. Addition of hydroxide, alkoxide, or amines led to the isolation of unstable crude ad- ducts, which reverted to the starting indenones on standing or in solution (10). Discussion The preparation of 3-cyano-3-phenyl-2-carboxamidoindanone (2a, Scheme 1) by the addition of cyanide to 1 has been previously reported (6).
    [Show full text]
  • At the Gabaa Receptor
    THE EFFECTS OF CHRONIC ETHANOL INTAKE ON THE ALLOSTERIC INTERACTION BE T WEEN GABA AND BENZODIAZEPINE AT THE GABAA RECEPTOR THESIS Presented to the Graduate Council of the University of North Texas in Partial Fulfillment of the Requirements For the Degree of MASTER OF SCIENCE By Jianping Chen, B.S., M.S. Denton, Texas May, 1992 Chen, Jianping, The Effects of Chronic Ethanol Intake on the Allsteric Interaction Between GABA and BenzodiazeDine at the GABAA Receptor. Master of Science (Biomedical Sciences/Pharmacology), May, 1992, 133 pp., 4 tables, 3.0 figures, references, 103 titles. This study examined the effects of chronic ethanol intake on the density, affinity, and allosteric modulation of rat brain GABAA receptor subtypes. In the presence of GABA, the apparent affinity for the benzodiazepine agonist flunitrazepam was increased and for the inverse agonist R015-4513 was decreased. No alteration in the capacity of GABA to modulate flunitrazepam and R015-4513 binding was observed in membranes prepared from cortex, hippocampus or cerebellum following chronic ethanol intake or withdrawal. The results also demonstrate two different binding sites for [3H]RO 15-4513 in rat cerebellum that differ in their affinities for diazepam. Chronic ethanol treatment and withdrawal did not significantly change the apparent affinity or density of these two receptor subtypes. ACKNOWLEDGEMENT I would like to express my sincere thanks to my major professor, Dr. Michael W. Martin. .I deeply appreciate his guidance and direction which initiated this study, and his kindness in sharing his laboratory facilities with me. His suggestions, patience, encouragement and support in the laboratory have contributed significantly to my understanding of the receptor mechanism of drug action.
    [Show full text]
  • Properties, Synthesis and Transformations Pedro M
    molecules Review ReviewStyrylpyrazoles: Properties, Synthesis and Styrylpyrazoles:Transformations Properties, Synthesis and Transformations Pedro M. O. Gomes, Pedro M. S. Ouro, Artur M. S. Silva * and Vera L. M. Silva * PedroLAQV-REQUIMTE, M. O. Gomes Department, Pedro M.of Chemistry, S. Ouro, Artur University M. S. of Silva Aveiro, * 3810-193and Vera Aveiro, L. M. Portugal; Silva * LAQV-REQUIMTE,[email protected] (P.M.O.G.); Department [email protected] of Chemistry, University(P.M.S.O.) of Aveiro, 3810-193 Aveiro, Portugal; [email protected]* Correspondence: (P.M.O.G.); [email protected] [email protected] (A.M.S.S.); (P.M.S.O.) [email protected] (V.L.M.S.); Tel.: +351-234-370714 (A.M.S.S.); * Correspondence:+351-234-370704 (V.L.M.S.) [email protected] (A.M.S.S.); [email protected] (V.L.M.S.); Tel.: +351-234-370714 (A.M.S.S.); +351-234-370704 (V.L.M.S.) Academic Editor: Derek J. McPhee Academic Editor: Derek J. McPhee Received: 21 November 2020; Accepted: 9 December 2020; Published: date Received: 21 November 2020; Accepted: 9 December 2020; Published: 12 December 2020 Abstract: The pyrazole nucleus and its reduced forms, pyrazolines and pyrazolidine, are privileged Abstract:scaffolds inThe medicinal pyrazole chemistry nucleus and due its to reduced their rema forms,rkable pyrazolines biological and activities. pyrazolidine, A huge are number privileged of scapyrazoleffolds inderivatives medicinal have chemistry been duestudied to their and remarkablereported over biological time. activities.This review A hugearticle number gives an of pyrazoleoverview derivatives of pyrazole have derivatives been studied that and contain reported a styryl over time.
    [Show full text]