DOCSLIB.ORG

Mail Order Madness

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mail Order Madness CASE STUDIES IN TOXICOLOGY Series Editor: Lewis S. Nelson, MD Case erate, effects. Dextrometho- A 14-year-old boy suffered a Mail Order rphan is found in cough and seizure shortly after he and cold preparations and is com- a friend smoked a substance monly abused by teenagers they ordered from an herbal Madness due to its accessibility as a products Web site. His friend nonprescription medication. called EMS before fleeing Nicholas Connors, MD, and Lewis S. Nelson, MD Herbal products like jimson- from the scene. Upon pre- weed (Datura stramonium), sentation to the ED, vital A 14-year-old boy has a seizure after yohimbine (Pausinystalia yo­ signs were: blood pressure, himbe), and Salvia divinorum 137/86 mm Hg; heart rate, smoking a substance he and a friend are readily available over the 143 beats/min; respiratory purchased through the Internet. Internet but do not generally rate, 20 breaths/min; temper- cause the combination of hy- ature, 100.0°F. Oxygen saturation was 99% on room air. peradrenergic vital-sign abnormalities and CNS effects On physical examination, he was awake, though laughing seen in this case. and making nonsensical word associations. He did not Synthetic cannabinoids such as “Spice” (also known as appear to be hallucinating, but did not respond appropri- “K2” or “potpourri”) and synthetic cathinones (“bath salts”) ately to questions. Abrasions were noted on his forehead, are also available through the Internet because of their un- and the pupils were dilated and reactive. His skin was certain legal status as products labeled, “not for human con- not flushed, diaphoretic, or dry. With the exception of sumption.” In addition to these agents, which have garnered tachycardia, cardiac, pulmonary, and abdominal exami- significant media and regulatory attention over the last sev- nations were normal. He had no focal motor or sensory eral years, substituted phenylethylamine derivatives also deficits or tremor, and motor tone was normal. Initial have potent psychoactive sympathomimetic effects. laboratory values were: finger-stick glucose, 210 mg/dL; sodium, 140 mEq/L; anion gap, 20 mEq/L. An electro- Case continuation cardiogram showed sinus tachycardia at 135 beats/min, When the patient’s parents arrived at the ED, they brought with a QRS duration of 80 ms and QTc interval of 453 ms. a small sheet of blotter paper, thought to be the source of the drug. Few drugs are sufficiently potent enough to be What could these boys have taken? distributed on blotter paper, which requires doses in the Abused substances that cause agitation, confusion, and microgram range. Examples include LSD, certain trypt- central nervous system (CNS) and cardiovascular ex- amines, and substituted phenylethylamines (4-bromo- citability are numerous and varied. Users of cocaine, 2,5-dimethoxyamphetamine; DOB). In this case, the label amphetamines, and methylxanthines present with symp- on the blotter paper suggested the nature of the agent. toms and signs characteristic of the sympathomimetic toxidrome, such as agitation, tachycardia, and hyperten- What are substituted phenylethylamines? sion. Additional sequelae of their use include hyperther- Phenylethylamines, also generally known as amphet- mia, seizure, dysrhythmia, and ischemia. amines, are organic compounds that function as CNS Although this patient was somewhat agitated, postic- neuromodulators. They have a clinical role as stimu- tal, and tachycardic, his mental status was suggestive of lants, psychedelics, antidepressants, decongestants, bron- a dissociative agent such as phencyclidine (PCP), ket- chodilators, and anorectics. The addition of functional amine, or dextromethorphan. PCP use may result in ex- groups to the backbone of the phenylethylamine mol- treme agitation and, at times, violent behavior; ketamine ecule may alter the clinical effects (both psychoactive and dextromethorphan produce similar, but more mod- and sympathomimetic) and pharmacokinetics of these 16 EMERGENCY MEDICINE | JULY 2013 www.emedmag.com drugs. (See the Figure on page effect. NBOMe is generally in- 18 for the chemical structure sufflated or applied to blotter of commonly abused sub- paper for buccal absorption. stituted phenylethylamines.) In one cohort, 57% pur- Substitutions along the ethyl- chased the substance through amine chain tend to enhance the Internet, and 83% used it the sympathomimetic effects in conjunction with other il- by stimulating the release of licit drugs.1 The most com- catecholamines such as do- mon subjective effects were pamine and norepinephrine changes in tactile, visual, and from presynaptic neurons. auditory perception. Trem- These substitutions make the bling, sweating, and blurry vi- © Shutterstock/ Stokkete Shutterstock/ © agent more “speedy.” In addi- sion were the most common tion, substitutions on the ring structure improve the ef- adverse effects.1 Case reports of intoxication with a 2C fects mediated by the serotonin receptors, making the agent describe recurrent seizures and serotonin toxicity,2 substance more psychoactive or “trippy.” With the substi- and fatal toxic leukoencephalopathy3 noted on magnetic tution of halogens along the ring structure, the agent typ- resonance imaging. Effects last about 4 to 8 hours.4 ically becomes more potent, and only microgram doses are needed to achieve the same “speedy” or “trippy” ef- What is the legal status of phenylethylamines? fects, or a combination of these. Phenylethylamines can The Controlled Substances Act of 1970 established the be taken orally, intravenously (IV), or through insuffla- Drug Enforcement Agency’s (DEA) five “schedules” of tion or inhalation. substances based on abuse potential, indications for med- The 2C series agents fall into the phenylethymamine ical use, and safety profile. Schedule I substances have a class and generally have the core structure of 3,4-meth- high potential for abuse and are deemed unsafe even un- ylenedioxy-N-methamphetamine (MDMA, “Ecstasy”) der medical supervision.5 Drugs such as heroin, lyser- with a substituted halogen on the six-carbon ring and gic acid diethylamide (LSD), mescaline, and marijuana methoxy side chains at the 2 and 5 positions on the ring are on the list of Schedule I substances. Additions to this structure. As noted, a halogen typically increases the sub- list include MDMA in 1985, gamma-hydroxybutyrate stance’s potency, and the methoxy groups on the ring (GHB) in 2000, and specific synthetic cannabinoids and enhance serotonergic activity, resulting in greater psy- synthetic cathinones in 2012. choactive affects. Of late, there has been a proliferation On January 4, 2013, certain substances within the class of synthetic products that vary slightly in their chemical of 2C drugs were designated Schedule I by the DEA.6 structure, with resulting unique clinical effects. However, a major difficulty with synthetic agents is the The 2,5-dimethoxy-N-(2-methoxybenzyl)phenyle- efforts of “street chemists’” to be “one step ahead” of le- thylamine (NBOMe) series of substances are structurally gal authorities. As each specific substance is banned, a similar to the 2C series but were not widely used before derivative or analog is synthesized, avoiding legal pros- 2010. The mechanism of action involves partial agonism ecution. Furthermore, it is difficult to ban an entire at the 5HT2A receptor, resulting in its enhanced “trippy” class of agents, and research into potential benefits of Dr Connors is a fellow of medical toxicology in the department of emergency medicine at the New York University School of Medicine and the New York City Poison Control Center. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also a member of the EMERGENCY MEDICINE editorial board. www.emedmag.com JULY 2013 | EMERGENCY MEDICINE 17 Case Studies in Toxicology ring-substituted amphetamines) and other causes of sei- Amphetamine Methamphetamine H NH zure. Measuring creatine kinase to assess for rhabdomy- 2 N olysis should be considered if there a history of prolonged immobilization or severe hyperthermia. Noncontrast MDMA 2C-I computed tomography (CT) of the head can be performed (3,4-methylenedioxy-N-methamphetamine) (2,5-dimethoxy-4-iodophenethylamine) in cases of altered mental status, particularly if there was H O O N head trauma or concerns for subarachnoid bleeding. Pa- NH2 O tients should be observed until symptoms abate and then I discharged home, as appropriate, after evaluation for sui- O cidality along with counseling on the dangers of drug use 25C-NBOMe (2-[4-chloro-2,5-dimethoxyphenyl]-N-[2-methoxybenzyl]ethanamine) and possible referral for drug treatment. O H N Case conclusion O Cl The patient received multiple doses of IV diazepam for O sedation. Upon waking the next day, he stated that he used 25C-NBOMe (2-[4-chloro-2,5-dimethoxyphenyl]- FIGURE Molecular structure of substituted N-[2-methoxybenzyl]ethanamine; also called “Pandora,” phenylethylamines. “Dime,” “Vortex,” “Cimbi-82”) on blotter paper for the first time on the day of presentation. He added that he substances can be stifled without significant justification. and his friend had ordered the drug from a synthetic- The Federal Analog Act of 1986 is an addition to the product Web site that advertised the substance as “le- Controlled Substances Act and addresses issues related gal LSD.” to “designer drugs.”7
Load more

Recommended publications
  • Pharmacology and Toxicology of Amphetamine and Related Designer Drugs
    Pharmacology and Toxicology of Amphetamine and Related Designer Drugs U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • Alcohol Drug Abuse and Mental Health Administration Pharmacology and Toxicology of Amphetamine and Related Designer Drugs Editors: Khursheed Asghar, Ph.D. Division of Preclinical Research National Institute on Drug Abuse Errol De Souza, Ph.D. Addiction Research Center National Institute on Drug Abuse NIDA Research Monograph 94 1989 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administration National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 For sale by the Superintendent of Documents, U.S. Government Printing Office Washington, DC 20402 Pharmacology and Toxicology of Amphetamine and Related Designer Drugs ACKNOWLEDGMENT This monograph is based upon papers and discussion from a technical review on pharmacology and toxicology of amphetamine and related designer drugs that took place on August 2 through 4, 1988, in Bethesda, MD. The review meeting was sponsored by the Biomedical Branch, Division of Preclinical Research, and the Addiction Research Center, 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 matieral 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.
    [Show full text]
  • Effect of Repeated MDMA Exposure on Rat Brain and Behaviour
    Effect of repeated MDMA exposure on rat brain and behaviour by Ross van de Wetering A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy Victoria University of Wellington, New Zealand 2020 Table of contents Absract ........................................................................................................................... 5 List of abbreviations ...................................................................................................... 7 CHAPTER 1: GENERAL INTRODUCTION ............................................................ 10 Introduction ........................................................................................................................ 10 Behavioural fundamentals of addiction ........................................................................... 12 Studying addiction ........................................................................................................... 13 Self-administration. ...................................................................................................... 14 Behavioural sensitisation. ............................................................................................ 18 Neurocircuitry of addiction ............................................................................................... 20 Ventral tegmental area and nucleus accumbens .............................................................. 20 Dopamine and reinforcement. .....................................................................................
    [Show full text]
  • Neuropharmacology and Toxicology of Novel Amphetamine-Type Stimulants
    Neuropharmacology and toxicology of novel amphetamine-type stimulants Bjørnar den Hollander Institute of Biomedicine, Pharmacology University of Helsinki Academic Dissertation To be presented, with the permission of the Medical Faculty of the University of Helsinki, for public examination in lecture hall 2, Biomedicum Helsinki 1, Haartmaninkatu 8, on January 16th 2015 at 10 am. Helsinki 2015 Supervisors Thesis committee Esa R. Korpi, MD, PhD Eero Castrén, MD, PhD Institute of Biomedicine, Pharmacology Neuroscience Center Faculty of Medicine University of Helsinki P.O. Box 63 (Haartmaninkatu 8) P.O. Box 56 (Viikinkaari 4) 00014 University of Helsinki, Finland 00014 University of Helsinki, Finland Esko Kankuri, MD, PhD Sari Lauri, PhD Institute of Biomedicine, Pharmacology Neuroscience Center and Faculty of Medicine Department of Biosciences/ Physiology P.O. Box 63 (Haartmaninkatu 8) University of Helsinki 00014 University of Helsinki, Finland P.O.Box 65 (Viikinkaari 1) 00014 University of Helsinki, Finland Reviewers Dissertation opponent Atso Raasmaja, Professor, PhD Prof David Nutt DM FRCP FRCPsych Division of Pharmacology and FMedSci Pharmacotherapy Edmond J. Safra Chair of Faculty of Pharmacy Neuropsychopharmacology P. O. Box 56 (Viikinkaari 5E) Division of Brain Sciences 00014 University of Helsinki, Finland Dept of Medicine Imperial College London Petri J. Vainio, MD, PhD Burlington Danes Building Pharmacology, Drug Development and Hammersmith Hospital Therapeutics Du Cane Road Institute of Biomedicine London W12 0NN, United Kingdom Faculty of Medicine Kiinamyllynkatu 10 C 20014 University of Turku, Finland The cover layout is done by Anita Tienhaara. The cover photo is by Edd Westmacott and shows a close-up of ecstasy tablets, photographed in Amsterdam in 2004.
    [Show full text]
  • Potentiation of Yohimbine-Induced Lethality in Mice: Predictor of Antidepressant Potential
    Drug Development Research 3:357-363 (1983) Potentiation of Yohimbine-Induced Lethality in Mice: Predictor of Antidepressant Potential Jeffrey B. Malick Biomedical Research Department, Stuart Pharmaceuticals, Division of ICI Americas, Inc., Wilmington, Delaware ABSTRACT Malick, J.B.: Potentiation of yohimbine-induced lethality in mice: Predictor of antidepres- sant potential. Drug Dev. Res. 3:357-363, 1983. The ability of antidepressant agents to potentiate the lethal or toxic effects of yohimbine in mice was evaluated. With very few exceptions, the antidepressants were the only agents that significantly enhanced yohimbine-induced lethality. All of the clinically effective anti- depressants, both typical (e.g., amine reuptake inhibitors, monoamine oxidase inhibitors) and atypical (e.g., mianserin, iprindole, bupropion, quipazine) drugs, produced a dose- related potentiation of yohimbine in mice. Representative anxiolytics and antipsychotics failed to potentiate yohimbine over a wide range of doses. Although several possible “false positives” (e.g., atropine, chlorpheniramine, and d-amphetamine) would be detected in this procedure, these same agents would be detected in other models (e.g., tetrabenazine antagonism, behavioral despair) considered predictive of antidepressant potential. Thus, the potentiation of yohimbine-induced lethality test in mice appears to represent a useful screening procedure for discovering potential antidepressant drugs. Key words: yohimbine, antidepressants, potentiation INTRODUCTION Antidepressants potentiate
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7,084,156 B2 Devita Et Al
    USOO7084156B2 (12) United States Patent (10) Patent No.: US 7,084,156 B2 DeVita et al. (45) Date of Patent: Aug. 1, 2006 (54) 2-AMINOQUINOLINE COMPOUNDS 2004/0106645 A1 6/2004 Blackburn et al. (75) Inventors: Robert J. DeVita, Westfield, NJ (US); FOREIGN PATENT DOCUMENTS Lehua Chang, Ramsey, NJ (US); EP O 252 503 11, 1992 Danny Chaung, Clark, NJ (US); MyLe JP 2001-226269 8, 2001 Hoang, Colonia, NJ (US); JinLong JP 371,059 12/2002 Jiang, Scotch Plains, NJ (US); Peter WO WO 96,284.46 9, 1996 Lin, Edison, NJ (US); Andreas W. WO WO 98.27815 7, 1998 Sailer, Edison, NJ (US); Jonathan R. WO WO99, 19326 4f1999 WO WO 99,42464 8, 1999 (73) Assignee: Merck & Co., Inc., Rahway, NJ (US) WO WO 99,48492 * 9, 1999 (*) Notice: Subject to any disclaimer, the term of this (Continued) patent is extended or adjusted under 35 U.S.C. 154(b) by 5 days. OTHER PUBLICATIONS Antelman et al., Chem. Abstract, 91:68543, Current Medical (21) Appl. No.: 10/496,615 Research and Opinion (1979), vol. 6, pp. 73-82, “ The (22) PCT Filed: Nov. 22, 2002 importance of stress in assessing the effects of anorectic e Afaf 9 drugs'. (86). PCT No.: PCT/USO2/37.556 (Continued) S 371 (c)(1), (2), (4) Date: May 25, 2004 Primary Examiner D. Margaret Seaman s 9 (74) Attorney, Agent, or Firm—Catherine D. Fitch; Melvin (87) PCT Pub. No.: WO03/045313 Winokur PCT Pub. Date: Jun. 5, 2003 (57) ABSTRACT (65) Prior Publication Data The present invention is concerned with compounds of the US 2005/OO26915 A1 Feb.
    [Show full text]
  • Mass Spectral, Infrared and Chromatographic Studies on Designer Drugs of the Piperazine Class by Karim M. Hafiz Abdel-Hay a Diss
    Mass Spectral, Infrared and Chromatographic Studies on Designer Drugs of the Piperazine Class by Karim M. Hafiz Abdel-Hay A dissertation submitted to the Graduate Faculty of Auburn University in partial fulfillment of the requirements for the degree of Doctor of Philosophy Auburn, Alabama May 7, 2012 Approved by C. Randall Clark, Chair, Professor of Pharmacal Sciences Jack DeRuiter, Professor of Pharmacal Sciences Forrest Smith, Associate Professor of Pharmacal Sciences Angela Calderon, Assistant Professor of Pharmacal Sciences Abstract The controlled drug 3,4-methylenedioxybenzylpiperazine (3,4-MDBP) has regioisomeric and isobaric substances of mass equivalence, which have similar analytical properties and thus the potential for misidentification. The direct regioisomers of 3,4-MDBP include the 2,3- methylenedioxy substitution pattern and the indirect regioisomers include the three ring substituted methoxybenzoylpiperazines. The ethoxy and methoxymethyl ring substituted benzylpiperazines constitute the major category of isobaric substances evaluated in this study. The direct and indirect regioisomers of 3,4-MDBP and also isobaric substances related to MDBP were synthesized and compared to 3,4-MDBP by using gas chromatographic and spectrophotometric techniques. The GC-MS studies of the direct regioisomers and isobaric substances of 3,4-MDBP indicated that they can not be easily differentiated by mass spectrometry. The synthesized compounds were converted to their perfluoroacyl derivatives, trifluoroacetyl (TFA), pentafluoropropionyl amides (PFPA) and heptafluorobutryl amides (HFBA), in an effort to individualize their mass spectra and to improve chromatographic resolution. Derivatized 3,4-MDBP was not distingushed from its derivatized regioisomers or isobars using mass spectrometry. No unique fragment ions were observed for the various regioisomeric and the isobaric compounds.
    [Show full text]
  • Screening of 300 Drugs in Blood Utilizing Second Generation
    Forensic Screening of 300 Drugs in Blood Utilizing Exactive Plus High-Resolution Accurate Mass Spectrometer and ExactFinder Software Kristine Van Natta, Marta Kozak, Xiang He Forensic Toxicology use Only Drugs analyzed Compound Compound Compound Atazanavir Efavirenz Pyrilamine Chlorpropamide Haloperidol Tolbutamide 1-(3-Chlorophenyl)piperazine Des(2-hydroxyethyl)opipramol Pentazocine Atenolol EMDP Quinidine Chlorprothixene Hydrocodone Tramadol 10-hydroxycarbazepine Desalkylflurazepam Perimetazine Atropine Ephedrine Quinine Cilazapril Hydromorphone Trazodone 5-(p-Methylphenyl)-5-phenylhydantoin Desipramine Phenacetin Benperidol Escitalopram Quinupramine Cinchonine Hydroquinine Triazolam 6-Acetylcodeine Desmethylcitalopram Phenazone Benzoylecgonine Esmolol Ranitidine Cinnarizine Hydroxychloroquine Trifluoperazine Bepridil Estazolam Reserpine 6-Monoacetylmorphine Desmethylcitalopram Phencyclidine Cisapride HydroxyItraconazole Trifluperidol Betaxolol Ethyl Loflazepate Risperidone 7(2,3dihydroxypropyl)Theophylline Desmethylclozapine Phenylbutazone Clenbuterol Hydroxyzine Triflupromazine Bezafibrate Ethylamphetamine Ritonavir 7-Aminoclonazepam Desmethyldoxepin Pholcodine Clobazam Ibogaine Trihexyphenidyl Biperiden Etifoxine Ropivacaine 7-Aminoflunitrazepam Desmethylmirtazapine Pimozide Clofibrate Imatinib Trimeprazine Bisoprolol Etodolac Rufinamide 9-hydroxy-risperidone Desmethylnefopam Pindolol Clomethiazole Imipramine Trimetazidine Bromazepam Felbamate Secobarbital Clomipramine Indalpine Trimethoprim Acepromazine Desmethyltramadol Pipamperone
    [Show full text]
  • “Rauwolscine/ Alfa Yohimbine”
    “Rauwolscine/ Alfa Yohimbine” Rauwolscine / Alfa Yohimbine – Natural and Safe Alternative for FAT BURNING Rauwolscine or Alfa–Yohimbine is an indole alkaloid with stimulant, aphrodisiac and local anaesthetic effects found naturally in plants of the genus Rauwolfia and Pausinystalia, along with several other active alkaloids including Yohimbine. Rauwolscine is a stereoisomer of Yohimbine, that is it is chemically identical, but differs in its 3 dimensional orientation. There are a total of 3 stereoisomers of Yohimbine, the other two are corynanthine and 3-epi-alpha-yohimbine. How it works – science behind this natural supplement Fat-Burning Potential Rauwolscine, or {3H}Rauwolscine, is a potent and selective antagonist of alpha-2 adrenergic receptors. This is the same mechanism by which yohimbine acts by blocking the pre- and post-synaptic alpha-2 adrenoceptors, this prevents the release of Norepinephrine from cells. Norepinepherine stimulates both the alpha and beta receptors in a cell. Stimulation of the beta adrenoceptors causes the breakdown of fat, whilst stimulating the alpha-2 adrenoceptors prevents this breakdown of fats.Alfa Yohimbine (Rauwolscine) blocks the alpha feedback mechanism, thus increasing norepinephrine. Additionally in blocking the alpha-2 receptor it blocks the storage of new fat. Serotonergic Effects Its works in a similar fashion like yohimbine, rauwolscine is an agonist of 5-HT1a/b receptors and induces serotonin-like effects.Whereas yohimbine has more affinity for the receptor, rauwolscine has a lower IC50 value (meaning it can saturate more receptors at the same dose) and can be seen as slightly more potent in serotonergic activity. Rauwolscine, an antagonist radioligand for the cloned human 5- hydroxytryptamine2b (5-HT2B) receptor.
    [Show full text]
  • Recreational Use, Analysis and Toxicity of Tryptamines
    Send Orders for Reprints to [email protected] 26 Current Neuropharmacology, 2015, 13, 26-46 Recreational Use, Analysis and Toxicity of Tryptamines Roberta Tittarelli1, Giulio Mannocchi1, Flaminia Pantano1 and Francesco Saverio Romolo1,2,* 1Legal Medicine Section, Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, “Sapienza” University of Rome, Viale Regina Elena, 336, 00161 Rome, Italy; 2Institut de Police Scientifique, Université de Lausanne, Batochime, 1015 Lausanne, Switzerland Abstract: The definition New psychoactive substances (NPS) refers to emerging drugs whose chemical structures are similar to other psychoactive compounds but not identical, representing a “legal” alternative to internationally controlled drugs. There are many categories of NPS, such as synthetic cannabinoids, synthetic cathinones, phenylethylamines, piperazines, ketamine derivatives and tryptamines. Tryptamines are naturally occurring compounds, which can derive from the amino acid tryptophan by several biosynthetic pathways: their structure is a combination of a benzene ring Roberta Tittarelli and a pyrrole ring, with the addition of a 2-carbon side chain. Tryptamines include serotonin and melatonin as well as other compounds known for their hallucinogenic properties, such as psilocybin in ‘Magic mushrooms’ and dimethyltryptamine (DMT) in Ayahuasca brews. Aim: To review the scientific literature regarding tryptamines and their derivatives, providing a summary of all the available information about the structure of these compounds, their effects in relationship with the routes of administration, their pharmacology and toxicity, including articles reporting cases of death related to intake of these substances. Methods: A comprehensive review of the published scientific literature was performed, using also non peer-reviewed information sources, such as books, government publications and drug user web fora.
    [Show full text]
  • The Role of Norepinephrine in the Pharmacology of 3,4
    !"#$%&'#$&($)&*#+,-#+"*,-#$,-$."#$/"0*102&'&34$&($ 56789#."4'#-#:,&;41#."01+"#.01,-#$<9=9>6$?#[email protected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`,E#-E$ I0--$ D-.#*$ 2*#0.,J#2&11&-@X&*3a',2#-2#@aY48-28 -:aSX]a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
    [Show full text]
  • SELECTIVE SEROTONIN REUPTAKE INHIBITORS SEXUAL FUNCTION K. Demyttenaere0 and D. Vanderschueren" University Hospital Gasthui
    * 1995 Elsevier Science B. V. All rights reserved. The Pharmacology of Sexual Function and Dysfunction J. Bancroft, editor 327 SELECTIVE SEROTONIN REUPTAKE INHIBITORS AND SEXUAL FUNCTION K. Demyttenaere0 and D. Vanderschueren" University Hospital Gasthuisberg (K.D. Leuven) ° Department of Psychiatry and Institute for Family and Sexological Sciences " Department of Endocrinology - Andrology Unit Herestraat 49 - B 3000 Leuven, Belgium dedicated to dr. Hugo De Cuyper (18.1.1946 - 13.9.1994) Introduction Selective Serotonin Reuptake Inhibitors (SSRIs : fluvoxamine -Floxyfral® or Fevarin®-, fluoxetine -Prozac®-, sertraline - Serlain® or Zoloft®-, paroxetine -Seroxat® or Paxil®- and citalopram -Cipramil®-) are potent and competitive inhibitors of the high affinity neuronal re-uptake mechanism for serotonin. These drugs also inhibit the re-uptake of noradrenaline and, generally to a lesser extent, dopamine, at higher concentrations. Paroxetine is the most potent serotonin uptake inhibitor in vitro of the drugs investigated, and citalopram is the most selective inhibitor of serotonin re-uptake, with paroxetine being more selective than fluoxetine, fluvoxamine and sertraline. Of the drugs investigated, only sertraline is a more potent inhibitor of dopamine compared with noradrenaline uptake. SSRIs are not only as effective as the tricyclic antidepressants in the treatment of major depression but are also effective in the treatment of obsessive-compulsive disorder, panic disorder, eating disorders and premenstrual syndrome (1). Although the latency of onset to therapeutic response seems to be somewhat longer, most psychiatrists consider SSRIs the initital drug of choice in the treatment of depressive disorders. Indeed, these drugs are usually better tolerated since they do not produce muscarinic, histaminic and alpha adrenergic side effects.
    [Show full text]
  • Yohimbine Enhances the Effect of Sildenafil on Erectile Process in Rats
    International Journal of Impotence Research (2008) 20, 409–417 & 2008 Nature Publishing Group All rights reserved 0955-9930/08 $30.00 www.nature.com/ijir ORIGINAL ARTICLE Yohimbine enhances the effect of sildenafil on erectile process in rats AM Senbel1 and T Mostafa2 1Pharmacology Department, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt and 2Andrology and Sexology Department, Faculty of Medicine, Cairo University, Cairo, Egypt Combining the centrally acting drug yohimbine with the peripheral conditioner sildenafil might be an approach to erectile dysfunction cases in which sildenafil alone failed. This work aimed to investigate the effect of yohimbine on sildenafil-induced facilitation of erectile process. Erectile responses to electrical stimulation of the cavernous nerve in anesthetized male rats were recorded. Intracavernosal pressure/systemic arterial pressure (ICP/SAP) was calculated, 1 and 5 min after intravenous administration of sildenafil, yohimbine or a combination of both. Changes in sexual arousal and copulatory performance indices were compared before and after these injections using behavioral mating experiments. It was shown that systemic administration of sildenafil produced a significant increase in ICP/SAP than control at doses X10 lmol kgÀ1. Yohimbine alone failed to potentiate erectile responses but yohimbine (1 lmol kgÀ1) significantly potentiated the effect of sildenafil 1–10 lmol kgÀ1 and 1 mmol kgÀ1, 1 and 5 min after injection. Potentiation of ICP/SAP induced by their combination was greater than the sum of the effects of the corresponding doses of either drug at the same time interval. A nonsignificant additional decrease in SAP than sildenafil- induced was observed if administered with yohimbine. Addition of sildenafil to yohimbine significantly enhanced the effect of the latter on intromission frequency, intercopulatory interval and the number of ejaculations per session.
    [Show full text]