DOCSLIB.ORG

Dual Mechanism Analgesia-Enhancing Agents

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Dual Mechanism Analgesia-Enhancing Agents Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2005 Dual Mechanism Analgesia-Enhancing Agents Shawquia Elithia Young Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Chemicals and Drugs Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/1166 This Thesis is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. O Shawquia Elithia Young, 2005 All Rights Reserved DUAL MECHANISM ANALGESIA-ENHANCING AGENTS A thesis submitted in partial fulfillment of the requiremehts for the degree of Master of Science at Virginia Commonwealth University. Shawquia Elithia Young Bachelor of Science, Hampton University, 2002 Director: Malgorzata Dukat, Ph.D. Department of Medicinal Chemistry Co-Director: Richard A. Glennon, Ph.D. Department of Medicinal Chemistry Virginia Commonwealth University Richmond, Virginia August 2005 Acknowledgements I would like to express my deepest gratitude to my'advisors Dr. Malgorzata Dukat and Dr. Richard Glennon for their wonderful guidance and teachings in the completion of this research. Their patience and honesty were greatly appreciated. I am also thankful to Dr. Anna Wesolowska for teaching me everything about the mouse tail-flick and hot- plate assays. I would like to thank Dr. Eliseu De Oliveira for being optimistic and patient while helping me in my synthesis. I want to give thanks to Dr. Richard Young for providing me with guidance in working with the locomotor activity assay. I appreciate Dr. Glennon's group for the help that they gave me throughout the years. I would like to thank the department of Medicinal Chemistry for offering me this wonderful opportunity to continue my education. On this long journey, my family helped motivate me with their neverending pep talks, love, and support. Thank you Mommy, Daddy, Malita, Shenita, and Wade, I love you all. I would like to give a special thanks to my mother because any decisions that I have made she always stood by me and told me that she was proud of me. I would like to thank my boyfriend Artis for his love, support, and encouragement. I definitely would like to say thank you to my friend Natasha Smith because she always listened to me and gave me good advice. Finally I would like to acknowledge and give thanks to Dr. Dukat, Dr. Glennon, and the School of Pharmacy for financial assistance. Table of Contents Page I . Acknowledgements .............................................................................................................11 . List of Tables .................................................................................................................... vll . List of Figures .................................................................................................................. vlll . List of Schemes ................................................................................................................. xi1 ... List of Abbreviations ....................................................................................................... xm Abstract ............................................................................................................................. xv I. Introduction ........................................................................................................1 11. Background ... .. .... .. .. ... .... ... .. .. .. .... .. .. .... .. .. .. ... .. .. .. .. .. .. .. .. .. .. .4 A. Pain ..........................................................................................................4 B. 5-HT3 Receptors .. .. .. .7 1. Classification ... .. ... ... .. .. ..... .. .. .. .. .... .. .. .. ... .. ... .. ... .. .. .. .. .. .. ..7 2. Structure .. .. .. .. .. .. ... ... ... .. .. .. ... .. .. .. ... ... .. ... .. .. .. .. .. .. .. .. .. .. .. ...9 3. Pharmacology ........................................... ........... ... .. ... ......... ............ 12 4. Ligands and Structure-Activity Relationships (SAR) ....... ............... 14 a) Agonists ........................................................... .... .. ................... ... 14 b) Antagonists ..... ..................................................... .............. ....... ... 19 C. a2-Adrenoceptors................................................................................... 30 1. Classification .................................................................................... 30 2. Structure .. .. .. .. .. .. .. .. .. .. ... .. .. .. .. .. .. .32 3 . Pharmacology ..................................................................................-36 4 . Ligands and SAR ............................... .'. ............................................ $38 a) Agonists ....................................................................................... 38 b) Antagonists ..................................................................................50 c) Therapeutic Applications of a2-Adrenoceptor Agents ...............55 D . Behavioral Tests for Nociception .......................................................... 64 111. Specific Aims and Rationale ............................................................................ 68 IV . Results and Discussion ....................................................................................76 A . Synthesis ................................................................................................76 a) N-(3-Chloropheny1)guanidine Nitrate (MD-354; 21) ......................76 b) Carbarnate analog of MD-354, 113.................................................. 77 c) N-(3-Methoxypheny1)guanidine Nitrate (26) ...................................81 d) A conformationally-constrained analog of MD-354, 114................ 82 B . Behavioral Studies .................................................................................86 1. Results .............................................................................................36 1 .1. MD-354 (21) ............................................................................. 86 1.1.1. Hot-plate assay ............................................................. 86 1 .l.2. Combination studies ..................................................... 88 1.l. 3. MorphineIMD-354 combination studies ......................89 1.2. N-(3,4, 5-Trichloropheny1)guanidine (29) ................................ 91 1.2.1. Tail-flick and hot-plate assays ......................................91 1.2.2. Combination studies .......'.. ............................................ 93 1.2.3. Mechanistic studies ...................................................... 95 1.2.4. Spontaneous activity .................................................102 1.3. The carbamate analog of MD-354, 113 .................................. 103 1.3.1. Tail-flick assay ........................................................... 103 1.3.2. Combination studies ...................................................105 1.4. N-(3-Methoxypheny1)guanidine (26) ..................................... 106 1.4.1. Tail-flick assay .......................................................... 106 1.4.2. Combination studies ...................................................107 2 . Discussion ...................................................................................... 109 V . Conclusions ....................................................................................................122 VI . Experimental ..................................................................................................124 A . Synthesis ..............................................................................................124 1. N-(3-Ch1orophenyl)guanidine Nitrate (MD-354) (21) .........................124 2 . N-(3-Methoxypheny1)guanidine Nitrate (26) ....................................... 125 3 . Methyl N-(3-chlorophenyl)guanidinecarboxylate Hydrochloride (113) .....................................................................................................125 4 . 2-Amino-5-chloro-3, 4-dihydroquinazoline Hydrobromide (114) ........ 126 5 . Dimethyl N,N'~(3~chlorophenyl)guanidinedicarboxylate(1 16) ..........127 6 . 2-Chloro-6-nitrobenzylbromide (1 19) ...................................................127 7 . 2-Chloro-6-nitrobenzylphthalimide (120) ............................................ 128 8 . 2-Chloro-6-nitrobenzylamine (121) ..................................................... 128 9 . 2-Amino-6-chlorobenzylamine (122) ...................................................128 B . Behavioral studies ................................................................................129 1 . Animals ................................................................................................129 2 . Drugs ...................................................................................................-130 3 . Behavioral assays .................................................................................130 a) Hot-plate assay ...............................................................................130 b) Tail-flick assay ...............................................................................131 c) Spontaneous activity ......................................................................132 d) Statistical analysis
Load more

Recommended publications
  • ALPHA ADRENOCEPTORS and HUMAN SEXUAL FUNCTION Alan
    8 1995 Elsevier Science B. V. All rights reserved. The Pharmacology of Sexual Function and Dysfunction J. Bancroft, editor 307 ALPHA ADRENOCEPTORS AND HUMAN SEXUAL FUNCTION Alan J Riley Field Place, Dunsmore, Buckinghamshire, HP22 6QH, UK Introduction Sexual functioning involves complex physiological processes which rely on the interplay of many central and peripheral neurotransmitter systems. Disturbances in any one of these systems might be associated with disturbed sexual function which, when recognised, may be alleviated by appropriate pharmacological manipulation, although at the present time this is more hypothesis than reality, The sympathetic nervous system is involved actively at various levels in the normal control of sexual responses. The effects of sympathetic activation are mediated by the release of noradrenaline from nerve terminals and the increased secretion of adrenaline from the adrenal medulla. These catecholamines selectively activate specific cellular sites in target tissues known as adrenoceptors (previously termed adrenergic receptors) to mediate responses. Almost fifty years ago, Alquist realised that tissue responses to catecholamines were mediated through two distinct types of receptors which he designated a and/? [1]. This review focuses on the involvement of a-adrenoceptors in human sexual functioning and dysfunction. Alpha adrenoceptors are located both pre- and post- synaptically and they were classified as either ar or af adrenoceptors according to location; or, being postsynaptic and az presynaptic. This classification continues to be used in some texts. However, as highly specific and selective pharmacological tools became available, this locational subclassification is found not always to be appropriate. Nowadays, classification of a-adrenoceptors is more appropriately based on pharmacological activity and additional subtypes of a-adrenoceptors have been identified by radioligand binding and molecular biological techniques [2].
    [Show full text]
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2012/0115729 A1 Qin Et Al
    US 201201.15729A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0115729 A1 Qin et al. (43) Pub. Date: May 10, 2012 (54) PROCESS FOR FORMING FILMS, FIBERS, Publication Classification AND BEADS FROM CHITNOUS BOMASS (51) Int. Cl (75) Inventors: Ying Qin, Tuscaloosa, AL (US); AOIN 25/00 (2006.01) Robin D. Rogers, Tuscaloosa, AL A6II 47/36 (2006.01) AL(US); (US) Daniel T. Daly, Tuscaloosa, tish 9.8 (2006.01)C (52) U.S. Cl. ............ 504/358:536/20: 514/777; 426/658 (73) Assignee: THE BOARD OF TRUSTEES OF THE UNIVERSITY OF 57 ABSTRACT ALABAMA, Tuscaloosa, AL (US) (57) Disclosed is a process for forming films, fibers, and beads (21) Appl. No.: 13/375,245 comprising a chitinous mass, for example, chitin, chitosan obtained from one or more biomasses. The disclosed process (22) PCT Filed: Jun. 1, 2010 can be used to prepare films, fibers, and beads comprising only polymers, i.e., chitin, obtained from a suitable biomass, (86). PCT No.: PCT/US 10/36904 or the films, fibers, and beads can comprise a mixture of polymers obtained from a suitable biomass and a naturally S3712). (4) (c)(1), Date: Jan. 26, 2012 occurring and/or synthetic polymer. Disclosed herein are the (2), (4) Date: an. AO. films, fibers, and beads obtained from the disclosed process. O O This Abstract is presented solely to aid in searching the sub Related U.S. Application Data ject matter disclosed herein and is not intended to define, (60)60) Provisional applicationpp No. 61/182,833,sy- - - s filed on Jun.
    [Show full text]
  • Effects of Dexfenfluramine and 5-HT3 Receptor Antagonists on Stress-Induced Reinstatement of Alcohol Seeking in Rats
    Psychopharmacology (2006) 186: 82–92 DOI 10.1007/s00213-006-0346-y ORIGINAL INVESTIGATION Anh Dzung Lê . Douglas Funk . Stephen Harding . W. Juzytsch . Paul J. Fletcher . Yavin Shaham Effects of dexfenfluramine and 5-HT3 receptor antagonists on stress-induced reinstatement of alcohol seeking in rats Received: 29 October 2005 / Accepted: 3 February 2006 / Published online: 7 March 2006 # Springer-Verlag 2006 Abstract Rationale and objectives: We previously found 0.1 mg/kg, i.p) on reinstatement induced by 10 min of that systemic injections of the 5-HT uptake blocker intermittent footshock (0.8 mA) was determined. fluoxetine attenuate intermittent footshock stress-induced Results: Systemic injections of dexfenfluramine, ondan- reinstatement of alcohol seeking in rats, while inhibition of setron or tropisetron attenuated footshock-induced rein- 5-HT neurons in the median raphe induces reinstatement statement of alcohol seeking. Injections of dexfenflur- of alcohol seeking. In this study, we further explored the amine, ondansetron, or tropisetron had no effect on role of 5-HT in footshock stress-induced reinstatement of extinguished lever responding in the absence of alcohol seeking by determining the effects of the 5-HT footshock. Conclusions: The present results provide releaser and reuptake blocker dexfenfluramine, and the 5- additional support for the hypothesis that brain 5-HT HT receptor antagonists ondansetron and tropisetron, which systems are involved in stress-induced reinstatement of decrease alcohol self-administration and anxiety-like re- alcohol seeking. The neuronal mechanisms that potentially sponses in rats, on this reinstatement. Methods: Different mediate the unexpected observation that both stimulation groups of male Wistar rats were trained to self-administer of 5-HT release and blockade of 5-HT3 receptors attenuate alcohol (12% v/v) for 28–31 days (1 h/day, 0.19 ml footshock-induced reinstatement are discussed.
    [Show full text]
  • Stems for Nonproprietary Drug Names
    USAN STEM LIST STEM DEFINITION EXAMPLES -abine (see -arabine, -citabine) -ac anti-inflammatory agents (acetic acid derivatives) bromfenac dexpemedolac -acetam (see -racetam) -adol or analgesics (mixed opiate receptor agonists/ tazadolene -adol- antagonists) spiradolene levonantradol -adox antibacterials (quinoline dioxide derivatives) carbadox -afenone antiarrhythmics (propafenone derivatives) alprafenone diprafenonex -afil PDE5 inhibitors tadalafil -aj- antiarrhythmics (ajmaline derivatives) lorajmine -aldrate antacid aluminum salts magaldrate -algron alpha1 - and alpha2 - adrenoreceptor agonists dabuzalgron -alol combined alpha and beta blockers labetalol medroxalol -amidis antimyloidotics tafamidis -amivir (see -vir) -ampa ionotropic non-NMDA glutamate receptors (AMPA and/or KA receptors) subgroup: -ampanel antagonists becampanel -ampator modulators forampator -anib angiogenesis inhibitors pegaptanib cediranib 1 subgroup: -siranib siRNA bevasiranib -andr- androgens nandrolone -anserin serotonin 5-HT2 receptor antagonists altanserin tropanserin adatanserin -antel anthelmintics (undefined group) carbantel subgroup: -quantel 2-deoxoparaherquamide A derivatives derquantel -antrone antineoplastics; anthraquinone derivatives pixantrone -apsel P-selectin antagonists torapsel -arabine antineoplastics (arabinofuranosyl derivatives) fazarabine fludarabine aril-, -aril, -aril- antiviral (arildone derivatives) pleconaril arildone fosarilate -arit antirheumatics (lobenzarit type) lobenzarit clobuzarit -arol anticoagulants (dicumarol type) dicumarol
    [Show full text]
  • Antihypertensive Agents Using ALZET Osmotic Pumps
    ALZET® Bibliography References on the Administration of Antihypertensive Agents Using ALZET Osmotic Pumps 1. Atenolol Q7652: W. B. Zhao, et al. Stimulation of beta-adrenoceptors up-regulates cardiac expression of galectin-3 and BIM through the Hippo signalling pathway. British Journal of Pharmacology 2019;176(14):2465-2481 Agents: Isoproterenol; propranolol; carvedilol; atenolol; ICI-118551 Vehicle: saline; ascorbic acid, buffered; Route: SC; Species: Mice; Pump: 2001; Duration: 1 day; 2 days; 7 days; ALZET Comments: Dose ((ISO 0.6, 6, 20 mg/kg/d), (Prop 2 mg/kg/d), (Carv 2 mg/kg/d), (AT 2 mg/kg/d), (ICI 1 mg/kg/d)); saline with 0.4 mM ascorbic acid used; Controls were non-transgenic and received mp w/ vehicle; animal info (12-16 weeks, Male, (C57BL/6J, beta2-TG, Mst1-TG, or dnMst1-TG)); ICI-118551 is a beta2-antagonist with the structure (2R,3S)-1-[(7-methyl-2,3-dihydro-1H-inden-4-yl)oxy]-3-(propan-2-ylamino)butan-2-ol; cardiovascular; Minipumps were removed to allow for washout of ISO overnight prior to imaging; Q7241: M. N. Nguyen, et al. Mechanisms responsible for increased circulating levels of galectin-3 in cardiomyopathy and heart failure. Sci Rep 2018;8(1):8213 Agents: Isoproterenol, Atenolol, ICI-118551 Vehicle: Saline, ascorbic acid; Route: SC; Species: Mice; Pump: Not Stated; Duration: 48 Hours; ALZET Comments: Dose: ISO (2, 6 or 30 mg/kg/day; atenolol (2 mg/kg/day), ICI-118551 (1 mg/kg/day); 0.4 mM ascorbic used; animal info (12 14 week-old C57Bl/6 mice); cardiovascular; Q6161: C.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2005/0049256A1 Lorton Et Al
    US 2005.0049256A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0049256A1 LOrton et al. (43) Pub. Date: Mar. 3, 2005 (54) TREATMENT OF INFLAMMATORY Publication Classification AUTOIMMUNE DISEASES WITH ALPHA-ADRENERGIC ANTAGONSTS AND BETA-ADRENERGICAGONSTS (51) Int. Cl." ...................... A61K 31/517; A61K 31/137 (76) Inventors: Dianne Lorton, Avondale, AZ (US); (52) U.S. Cl. ..................... 514/252.17; 514/649; 514/651 Cheri Lubahn, Glendale, AZ (US) Correspondence Address: JENNINGS, STROUSS & SALMON, P.L.C. (57) ABSTRACT 201 E. WASHINGTON ST, 11TH FLOOR PHOENIX, AZ 85004 (US) The present invention discloses a novel compound and (21) Appl. No.: 10/928,437 method for the treatment of inflammatory autoimmune dis eases, for example, rheumatoid arthritis, using C.-adrenergic (22) Filed: Aug. 27, 2004 antagonists and B-adrenergic agonists in combination. Treat ment of animals, namely humans, with an O-adrenergic Related U.S. Application Data antagonist, preferably, phentolamine, and a B-adrenergic agonist, preferably terbutaline, in combination can Signifi (60) Provisional application No. 60/498.367, filed on Aug. cantly Suppress the joint destruction and inflammation due to 27, 2003. disease in these animals. Patent Application Publication Mar. 3, 2005 Sheet 1 of 5 US 2005/0049256A1 Patent Application Publication Mar. 3, 2005 Sheet 2 of 5 US 2005/0049256A1 e \ s o o (ulu) pA ped)00 IBuedos. IOC Patent Application Publication Mar. 3, 2005 Sheet 3 of 5 US 2005/0049256A1 as o N w N o et N O CY) c5 O t al L cN Y D. a s t is r s re y (uu) supW pedoo Patent Application Publication US 2005/004925.6 A1 |0*>d 0|| eIOOS 3 guide foupe Patent Application Publication Mar.
    [Show full text]
  • And Antagonists Between the Pithed Rabbit and Rat J.M
    Br. J. Pharmac. (1987), 91, 457-466 Difference in the potency ofa2-adrenoceptor agonists and antagonists between the pithed rabbit and rat J.M. Bulloch, 'J.R. Docherty, 2N.A. Flavahan, J.C. McGrath & C.E. McKean Institute ofPhysiology, University ofGlasgow, Glasgow G12 8QQ, Scotland 1 The subtypes ofa-adrenoceptors which mediate pressor responses to sympathomimetic agonists or to nerve stimulation in pithed rabbits have been classified according to the effects of 'selective' antagonists and a comparison has been made, for the xt2-subtype, with corresponding responses in the rat. 2 In the rabbit the dose-response curve for phenylephrine was shifted to the right in parallel by prazosin (1 mg kg-') and was unaffected by rauwolscine (1 mg kg '). The dose-response curve for noradrenaline was shifted to the right by prazosin (I mg kg -') and was shifted to a smaller extent by rauwolscine (1 mg kg -') or imiloxan (1Omg kg-'). After rauwolscine, prazosin produced a rightward shift larger than when given alone. After prazosin, rauwolscine produced a rightward shift larger than when given alone. 3 The responses to pressor nerve stimulation at low frequencies (< 1 Hz) could be reduced by prazosin, rauwolscine or imiloxan but those at a higher frequency could be reduced only by prazosin. 4 These results indicate that the responses to noradrenaline or to nerve stimulation are mediated by both a,- and a2-adrenoceptors. Low doses or frequencies have a proportionately greater component which is M2 5 Responses to noradrenaline after prazosin (1 mg kg -'), were sufficiently sensitive to rauwolscine to be considered as predominantly a2.
    [Show full text]
  • (R)-Zacopride Or a Salt Thereof for the Manufacture of a Medicament for the Treatment of Sleep Apnea
    Europäisches Patentamt *EP001090638A1* (19) European Patent Office Office européen des brevets (11) EP 1 090 638 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.7: A61K 31/439, A61P 25/00 11.04.2001 Bulletin 2001/15 (21) Application number: 99120169.0 (22) Date of filing: 08.10.1999 (84) Designated Contracting States: (72) Inventor: Depoortere, Henri AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU 78720 Cernay-La-Ville (FR) MC NL PT SE Designated Extension States: (74) Representative: Thouret-Lemaitre, Elisabeth et al AL LT LV MK RO SI Sanofi-Synthélabo Service Brevets (71) Applicant: SANOFI-SYNTHELABO 174, avenue de France 75013 Paris (FR) 75013 Paris (FR) (54) Use of (R)-zacopride or a salt thereof for the manufacture of a medicament for the treatment of sleep apnea (57) The present invention relates to the use of (R)- zacopride or a salt thereof in the manufacture of drugs intended for the treatment of sleep apnea. EP 1 090 638 A1 Printed by Jouve, 75001 PARIS (FR) EP 1 090 638 A1 Description [0001] The present invention relates to the use of (R)-zacopride or a pharmaceutically acceptable salts thereof for the manufacture of drugs intended for the treatment of sleep apnea. 5 [0002] Obstructuve sleep apnea (OSA), as defined by the presence of repetitive upper airway obstruction during sleep, has been identified in as many as 24% of working adult men, and 9% of similar women (Young et al., The occurence of sleep-disordered breathing among middle-aged adults., New England, J.
    [Show full text]
  • Hallucinogens: an Update
    National Institute on Drug Abuse RESEARCH MONOGRAPH SERIES Hallucinogens: An Update 146 U.S. Department of Health and Human Services • Public Health Service • National Institutes of Health Hallucinogens: An Update Editors: Geraline C. Lin, Ph.D. National Institute on Drug Abuse Richard A. Glennon, Ph.D. Virginia Commonwealth University NIDA Research Monograph 146 1994 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 ACKNOWLEDGEMENT This monograph is based on the papers from a technical review on “Hallucinogens: An Update” held on July 13-14, 1992. The review meeting was sponsored by the National Institute on Drug Abuse. COPYRIGHT STATUS The National Institute on Drug Abuse has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required. All other material in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors. Citation of the source is appreciated. Opinions expressed in this volume are those of the authors and do not necessarily reflect the opinions or official policy of the National Institute on Drug Abuse or any other part of the U.S. Department of Health and Human Services. The U.S. Government does not endorse or favor any specific commercial product or company.
    [Show full text]
  • Rat Animal Models for Screening Medications to Treat Alcohol Use Disorders
    ACCEPTED MANUSCRIPT Selectively Bred Rats Page 1 of 75 Rat Animal Models for Screening Medications to Treat Alcohol Use Disorders Richard L. Bell*1, Sheketha R. Hauser1, Tiebing Liang2, Youssef Sari3, Antoinette Maldonado-Devincci4, and Zachary A. Rodd1 1Indiana University School of Medicine, Department of Psychiatry, Indianapolis, IN 46202, USA 2Indiana University School of Medicine, Department of Gastroenterology, Indianapolis, IN 46202, USA 3University of Toledo, Department of Pharmacology, Toledo, OH 43614, USA 4North Carolina A&T University, Department of Psychology, Greensboro, NC 27411, USA *Send correspondence to: Richard L. Bell, Ph.D.; Associate Professor; Department of Psychiatry; Indiana University School of Medicine; Neuroscience Research Building, NB300C; 320 West 15th Street; Indianapolis, IN 46202; e-mail: [email protected] MANUSCRIPT Key Words: alcohol use disorder; alcoholism; genetically predisposed; selectively bred; pharmacotherapy; family history positive; AA; HAD; P; msP; sP; UChB; WHP Chemical compounds studied in this article Ethanol (PubChem CID: 702); Acamprosate (PubChem CID: 71158); Baclofen (PubChem CID: 2284); Ceftriaxone (PubChem CID: 5479530); Fluoxetine (PubChem CID: 3386); Naltrexone (PubChem CID: 5360515); Prazosin (PubChem CID: 4893); Rolipram (PubChem CID: 5092); Topiramate (PubChem CID: 5284627); Varenicline (PubChem CID: 5310966) ACCEPTED _________________________________________________________________________________ This is the author's manuscript of the article published in final edited form as: Bell, R. L., Hauser, S. R., Liang, T., Sari, Y., Maldonado-Devincci, A., & Rodd, Z. A. (2017). Rat animal models for screening medications to treat alcohol use disorders. Neuropharmacology. https://doi.org/10.1016/j.neuropharm.2017.02.004 ACCEPTED MANUSCRIPT Selectively Bred Rats Page 2 of 75 The purpose of this review is to present animal research models that can be used to screen and/or repurpose medications for the treatment of alcohol abuse and dependence.
    [Show full text]
  • Marrakesh Agreement Establishing the World Trade Organization
    No. 31874 Multilateral Marrakesh Agreement establishing the World Trade Organ ization (with final act, annexes and protocol). Concluded at Marrakesh on 15 April 1994 Authentic texts: English, French and Spanish. Registered by the Director-General of the World Trade Organization, acting on behalf of the Parties, on 1 June 1995. Multilat ral Accord de Marrakech instituant l©Organisation mondiale du commerce (avec acte final, annexes et protocole). Conclu Marrakech le 15 avril 1994 Textes authentiques : anglais, français et espagnol. Enregistré par le Directeur général de l'Organisation mondiale du com merce, agissant au nom des Parties, le 1er juin 1995. Vol. 1867, 1-31874 4_________United Nations — Treaty Series • Nations Unies — Recueil des Traités 1995 Table of contents Table des matières Indice [Volume 1867] FINAL ACT EMBODYING THE RESULTS OF THE URUGUAY ROUND OF MULTILATERAL TRADE NEGOTIATIONS ACTE FINAL REPRENANT LES RESULTATS DES NEGOCIATIONS COMMERCIALES MULTILATERALES DU CYCLE D©URUGUAY ACTA FINAL EN QUE SE INCORPOR N LOS RESULTADOS DE LA RONDA URUGUAY DE NEGOCIACIONES COMERCIALES MULTILATERALES SIGNATURES - SIGNATURES - FIRMAS MINISTERIAL DECISIONS, DECLARATIONS AND UNDERSTANDING DECISIONS, DECLARATIONS ET MEMORANDUM D©ACCORD MINISTERIELS DECISIONES, DECLARACIONES Y ENTEND MIENTO MINISTERIALES MARRAKESH AGREEMENT ESTABLISHING THE WORLD TRADE ORGANIZATION ACCORD DE MARRAKECH INSTITUANT L©ORGANISATION MONDIALE DU COMMERCE ACUERDO DE MARRAKECH POR EL QUE SE ESTABLECE LA ORGANIZACI N MUND1AL DEL COMERCIO ANNEX 1 ANNEXE 1 ANEXO 1 ANNEX
    [Show full text]