DOCSLIB.ORG

Amphetamine, 3,4

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Amphetamine, 3,4 0026-895X/01/6006-1181–1188$3.00 MOLECULAR PHARMACOLOGY Vol. 60, No. 6 Copyright © 2001 The American Society for Pharmacology and Experimental Therapeutics 1304/951292 Mol Pharmacol 60:1181–1188, 2001 Printed in U.S.A. ACCELERATED COMMUNICATION Amphetamine, 3,4-Methylenedioxymethamphetamine, Lysergic Acid Diethylamide, and Metabolites of the Catecholamine Neurotransmitters Are Agonists of a Rat Trace Amine Receptor JAMES R. BUNZOW, MARK S. SONDERS, SEKSIRI ARTTAMANGKUL, LAURA M. HARRISON, GE ZHANG, DENISE I. QUIGLEY, TRISTAN DARLAND, KATHERINE L. SUCHLAND, SHAILAJA PASUMAMULA, JAMES L. KENNEDY, SUSAN B. OLSON, R. ELLEN MAGENIS, SUSAN G. AMARA, and DAVID K. GRANDY Departments of Physiology & Pharmacology (J.R.B., S.A., L.M.H., G.Z., D.I.Q., T.D., K.L.S., S.P., S.B.O., R.E.M., D.K.G.) and Molecular and Medical Genetics (S.B.O., R.E.M), School of Medicine, the Vollum Institute (M.S.S., S.G.A.), and the Howard Hughes Medical Institute (S.G.A.), Oregon Health & Science University, Portland, Oregon; and Centre for Addiction and Mental Health, University of Toronto, Canada (J.L.K.) Received August 21, 2001; accepted September 28, 2001 This paper is available online at http://molpharm.aspetjournals.org ABSTRACT The trace amine para-tyramine is structurally and functionally re- goline derivatives, adrenergic ligands, and 3-methylated metabo- lated to the amphetamines and the biogenic amine neurotrans- lites of the catecholamine neurotransmitters are also good ago- mitters. It is currently thought that the biological activities elicited nists at the rat trace amine receptor 1 (rTAR1). These results by trace amines such as p-tyramine and the psychostimulant suggest that the trace amines and catecholamine metabolites amphetamines are manifestations of their ability to inhibit the may serve as the endogenous ligands of a novel intercellular clearance of extracellular transmitter and/or stimulate the efflux of signaling system found widely throughout the vertebrate brain and transmitter from intracellular stores. Here we report the discovery periphery. Furthermore, the discovery that amphetamines, includ- and pharmacological characterization of a rat G protein-coupled ing 3,4-methylenedioxymethamphetamine (MDMA; “ecstasy”), receptor that stimulates the production of cAMP when exposed to are potent rTAR1 agonists suggests that the effects of these the trace amines p-tyramine, ␤-phenethylamine, tryptamine, and widely used drugs may be mediated in part by this receptor as well octopamine. An extensive pharmacological survey revealed that as their previously characterized targets, the neurotransmitter psychostimulant and hallucinogenic amphetamines, numerous er- transporter proteins. In vertebrates, the trace amines ␤-phenethylamine (Boulton and Dyck, 1974; Tallman et al., 1976). The trace (␤-PEA), para-tyramine, tryptamine, and octopamine are amines are found in low amounts (accounting for less than found in peripheral tissues as well as the central nervous 1% of the biogenic amines in most brain regions) and have system (Tallman et al., 1976; Paterson et al., 1990). In vivo, been thought of as metabolic byproducts of catecholamine ␤-PEA and p-tyramine can be synthesized from phenylala- biosynthesis. Investigations into the effects of trace amines nine or tyrosine by the enzyme amino acid decarboxylase. on smooth muscle and glandular preparations early in the twentieth century clearly demonstrated that amines pro- This work was supported by National Institute on Drug Abuse (NIDA) duced by putrefaction and lacking the catechol nucleus were Grants DA10703 and DA12408, NIDA/National Institute on Alcohol Abuse capable of producing robust sympathomimetic effects (Barger and Alcoholism Training Grant DA07262-09, and the Howard Hughes Medical Institute. and Dale, 1910). Currently it is thought that p-tyramine and 1 Because the predicted amino acid sequences of the rat and human trace ␤-PEA manifest their peripheral effects by promoting the amine receptors described here are identical to the rTAR1 and hTAR1 se- quences reported by Borowsky et al. (2001), we employ the same nomencla- efflux of catecholamines from sympathetic neurons and adre- ture. nals (Schonfeld and Trendelenburg, 1989; Mundorf et al., ABBREVIATIONS: ␤-PEA, ␤–phenethylamine; MDMA, 3,4-methylenedioxymethamphetamine; GPCR, G protein-coupled receptor; 5-HT, 5-hy- droxytryptamine (serotonin); 3-MT, 3-methoxytyramine (3-methyldopamine); TAR1, trace amine receptor 1; PCR, polymerase chain reaction; RT, reverse transcription; HEK, human embryonic kidney; KRH, Krebs-Ringer-HEPES; PBS, phosphate-buffered saline; BAC, bacterial artificial chromosome; DA, dopamine; NE, norepinephrine; Epi, epinephrine; COMT, catechol-O-methyltransferase; DOI, 2-amino,1-(2,5-dimethoxy-4- iodophenyl)propane. 1181 1182 Bunzow et al. 1999) which results in the indirect stimulation of adrenergic Biomedical Research, Oregon Health and Science University). All receptors (Black et al., 1980). The abilities of p-tyramine and other drugs were purchased from Sigma Chemical Co. (St. Louis, ␤-PEA to deplete neurotransmitter from storage vesicles, MO), Aldrich (Milwaukee, WI), Tocris Cookson Inc. (Ballwin, MO), or compete with neurotransmitters for uptake, and stimulate Alltech Associates (State College, PA). outward neurotransmitter flux through the plasma mem- Cloning and Expression of Nucleic Acids. First strand cDNA was synthesized from the rat pancreatic tumor cell line AR42J brane carriers are similar to the actions of the ␤-PEA analog, ␣ ␤ (American Type Culture Collection, Manassas, VA) and was used as -methyl- -phenethylamine, better known as amphetamine a template for the original polymerase chain reactions (PCRs) em- (Seiden et al., 1993; Amara and Sonders, 1998). ploying a pair of degenerate oligonucleotide primers based on a Amphetamines were originally marketed as stimulants derived consensus sequence of the third and sixth transmembrane and appetite suppressants, but their clinical use is now domains of known members of the catecholamine receptor family: mostly limited to treating attention deficit hyperactivity dis- primer TM III, 5Ј-GAGTCGACCTGTG(C/T)G(C/T)(C/G)AT(C/T)(A/ order (Seiden et al., 1993). Although listed as controlled G)CIIT(G/T)GAC(C/A)G(C/G)TAC-3Ј; primer TM VI, 5Ј-CAGAAT- substances, amphetamines are widely consumed because of TCAG(T/A)AGGGCAICCAGCAGAI(G/C)(G/A)(T/C)GAA-3Ј (where their ability to produce wakefulness and intense euphoria. I ϭ inosine). Some substituted amphetamines, such as MDMA (“ecstasy”) The conditions used were: 94°C for 90 s, 50°C for 90 s, and 72°C for and DOI, are taken for their “empathogenic” and hallucino- 120 s, for 35 cycles. Products from 400 to 750 base pairs were purified from a 1.0% agarose gel using Prep-A-Gene (Bio-Rad, Hercules, CA), genic effects. (Shulgin and Shulgin, 1991; Eisner, 1994). Nu- digested with EcoRI and SalI, and subcloned into the vector pBlue- merous liabilities are associated with the use of amphet- script (Stratagene, La Jolla, CA). Plasmid DNA from these clones amines, including hyperthermia (Byard et al., 1998), was purifed, and the nucleotide sequence of the insert was deter- neurotoxicity (Ricaurte and McCann, 1992), psychosis (Sei- mined by the dideoxynucleotide chain termination method. The de- den et al., 1993), and psychological dependence (Murray, duced amino acid sequence of a 0.4-kilobase PCR fragment displayed 1998). In addition to the actions of amphetamines at biogenic regions of homology to the known catecholamine receptors. This amine transporters, it is also clear that a subset of amphet- clone was subsequently labeled with 32P and used to probe a rat amine analogs, especially those with hallucinogenic proper- genomic library (CLONTECH, Palo Alto, CA) that had been trans- ties, can act directly on 5-HT receptors because they have ferred to nylon membranes (Gene Screen Plus; PerkinElmer Life much higher affinities for these sites than for the transport- Science Products, Boston, MA) resulting in the identification of sev- eral full-length clones. Full-length clones were also obtained by RT- ers (Marek and Aghajanian, 1998). PCR from the rat pancreatic tumor cell line RIN5 and rat cerebel- We report herein the discovery and functional expression lum. The nucleotide sequence of the human TAR has been assigned of a rat G protein-coupled receptor with homology to mem- GenBank accession number AF200627. The nucleotide sequence of bers of the catecholamine receptor family. This receptor stim- the rat TAR has been assigned GenBank accession number ulates cAMP production when exposed to the trace amines AF421352. p-tyramine and ␤-PEA. A pharmacological survey revealed For the purpose of expressing the putative receptor in tissue that this rat trace amine receptor (rTAR1) is directly acti- culture, a 16-amino-acid signal sequence from the influenza hemag- vated by a wide variety of clinically and socially important glutinin virus followed by the 8-amino-acid M1-“Flag” epitope and a drugs, which include amphetamines, ergot derivatives, and “MetGly” linker were added to the N terminus of the cerebellar adrenergic agents. Surprisingly, rTAR1 is more potently ac- cDNA before its insertion into the expression vector pcDNA3.1/V5/ His-TOPO (Invitrogen). The resulting construct was transiently ex- tivated by the presumably “inactive” catecholamine metabo- pressed in HEK293 and COS-7 cells after LipofectAMINE-assisted lites 3-methoxytyramine (3-MT), normetanephrine, and transfection (Invitrogen). A line of G418 resistant HEK293 cells
Load more

Recommended publications
  • Neurotransmitter Resource Guide
    NEUROTRANSMITTER RESOURCE GUIDE Science + Insight doctorsdata.com Doctor’s Data, Inc. Neurotransmitter RESOURCE GUIDE Table of Contents Sample Report Sample Report ........................................................................................................................................................................... 1 Analyte Considerations Phenylethylamine (B-phenylethylamine or PEA) ................................................................................................. 1 Tyrosine .......................................................................................................................................................................................... 3 Tyramine ........................................................................................................................................................................................4 Dopamine .....................................................................................................................................................................................6 3, 4-Dihydroxyphenylacetic Acid (DOPAC) ............................................................................................................... 7 3-Methoxytyramine (3-MT) ............................................................................................................................................... 9 Norepinephrine ........................................................................................................................................................................
    [Show full text]
  • Methylphenidate Hydrochloride
    Application for Inclusion to the 22nd Expert Committee on the Selection and Use of Essential Medicines: METHYLPHENIDATE HYDROCHLORIDE December 7, 2018 Submitted by: Patricia Moscibrodzki, M.P.H., and Craig L. Katz, M.D. The Icahn School of Medicine at Mount Sinai Graduate Program in Public Health New York NY, United States Contact: [email protected] TABLE OF CONTENTS Page 3 Summary Statement Page 4 Focal Point Person in WHO Page 5 Name of Organizations Consulted Page 6 International Nonproprietary Name Page 7 Formulations Proposed for Inclusion Page 8 International Availability Page 10 Listing Requested Page 11 Public Health Relevance Page 13 Treatment Details Page 19 Comparative Effectiveness Page 29 Comparative Safety Page 41 Comparative Cost and Cost-Effectiveness Page 45 Regulatory Status Page 48 Pharmacoepial Standards Page 49 Text for the WHO Model Formulary Page 52 References Page 61 Appendix – Letters of Support 2 1. Summary Statement of the Proposal for Inclusion of Methylphenidate Methylphenidate (MPH), a central nervous system (CNS) stimulant, of the phenethylamine class, is proposed for inclusion in the WHO Model List of Essential Medications (EML) & the Model List of Essential Medications for Children (EMLc) for treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) under ICD-11, 6C9Z mental, behavioral or neurodevelopmental disorder, disruptive behavior or dissocial disorders. To date, the list of essential medications does not include stimulants, which play a critical role in the treatment of psychotic disorders. Methylphenidate is proposed for inclusion on the complimentary list for both children and adults. This application provides a systematic review of the use, efficacy, safety, availability, and cost-effectiveness of methylphenidate compared with other stimulant (first-line) and non-stimulant (second-line) medications.
    [Show full text]
  • Review Paper Monoamine Oxidase Inhibitors: a Review Concerning Dietary Tyramine and Drug Interactions
    PsychoTropical Commentaries (2016) 1:1 – 90 © Fernwell Publications Review Paper Monoamine Oxidase Inhibitors: a Review Concerning Dietary Tyramine and Drug Interactions PK Gillman PsychoTropical Research, Bucasia, Queensland, Australia Abstract This comprehensive monograph surveys original data on the subject of both dietary tyramine and drug interactions relevant to Monoamine Oxidase Inhibitors (MAOIs), about which there is much outdated, incorrect and incomplete information in the medical literature and elsewhere. Fewer foods than previously supposed have problematically high tyramine levels because international food hygiene regulations have improved both production and handling. Cheese is the only food that has, in the past, been associated with documented fatalities from hypertension, and now almost all ‘supermarket’ cheeses are perfectly safe in healthy-sized portions. The variability of sensitivity to tyramine between individuals, and the sometimes unpredictable amount of tyramine content in foods, means a little knowledge and care are still advised. The interactions between MAOIs and other drugs are now well understood, are quite straightforward, and are briefly summarized here (by a recognised expert). MAOIs have no apparently clinically relevant pharmaco-kinetic interactions, and the only significant pharmaco-dynamic interaction, other than the ‘cheese reaction’ (caused by indirect sympatho-mimetic activity [ISA], is serotonin toxicity ST (aka serotonin syndrome) which is now well defined and straightforward to avoid by not co-administering any drug with serotonin re-uptake inhibitor (SRI) potency. There are no therapeutically used drugs, other than SRIs, that are capable of inducing serious ST with MAOIs. Anaesthesia is not contra- indicated if a patient is taking MAOIs. Most of the previously held concerns about MAOIs turn out to be mythical: they are either incorrect, or over-rated in importance, or stem from apprehensions born out of insufficient knowledge.
    [Show full text]
  • Download Product Insert (PDF)
    PRODUCT INFORMATION Tyramine Item No. 18601 CAS Registry No.: 51-67-2 Formal Name: 4-(2-aminoethyl)-phenol Synonyms: 2-(4-Hydroxyphenyl)ethylamine, NSC 249188, p-Tyramine, NH2 Uteramine MF: C8H11NO FW: 137.2 HO Purity: ≥98% UV/Vis.: λmax: 224, 278 nm Supplied as: A crystalline solid Storage: -20°C Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures Tyramine is supplied as a crystalline solid. A stock solution may be made by dissolving the tyramine in the solvent of choice. Tyramine is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide (DMF), which should be purged with an inert gas. The solubility of tyramine in these solvents is approximately 5, 20, and 25 mg/ml, respectively. Tyramine is sparingly soluble in aqueous buffers. For maximum solubility in aqueous buffers, tyramine should first be dissolved in DMF and then diluted with the aqueous buffer of choice. Tyramine has a solubility of approximately 0.5 mg/ml in a 1:1 solution of DMF:PBS (pH 7.2) using this method. We do not recommend storing the aqueous solution for more than one day. Description Tyramine is a tyrosine-derived endogenous and dietary monoamine and trace amine-associated receptor 1-3 1 (TAAR1) agonist. It activates TAAR1 (EC50s = 0.08, 0.69, and 2.26 µM for rat, mouse, and human-rat chimera receptors, respectively).1 Tyramine also inhibits the release of norepinephrine and dopamine in 4 isolated rat caudate nucleus (IC50s = 40.6 and 119 nM, respectively).
    [Show full text]
  • Ayahuasca: Spiritual Pharmacology & Drug Interactions
    Ayahuasca: Spiritual Pharmacology & Drug Interactions BENJAMIN MALCOLM, PHARMD, MPH [email protected] MARCH 28 TH 2017 AWARE PROJECT Can Science be Spiritual? “Science is not only compatible with spirituality; it is a profound source of spirituality. When we recognize our place in an immensity of light years and in the passage of ages, when we grasp the intricacy, beauty and subtlety of life, then that soaring feeling, that sense of elation and humility combined, is surely spiritual. The notion that science and spirituality are somehow mutually exclusive does a disservice to both.” – Carl Sagan Disclosures & Disclaimers No conflicts of interest to disclose – I don’t get paid by pharma and have no potential to profit directly from ayahuasca This presentation is for information purposes only, none of the information presented should be used in replacement of medical advice or be considered medical advice This presentation is not an endorsement of illicit activity Presentation Outline & Objectives Describe what is known regarding ayahuasca’s pharmacology Outline adverse food and drug combinations with ayahuasca as well as strategies for risk management Provide an overview of spiritual pharmacology and current clinical data supporting potential of ayahuasca for treatment of mental illness Pharmacology Terms Drug ◦ Term used synonymously with substance or medicine in this presentation and in pharmacology ◦ No offense intended if I call your medicine or madre a drug! Bioavailability ◦ The amount of a drug that enters the body and is able to have an active effect ◦ Route specific: bioavailability is different between oral, intranasal, inhalation (smoked), and injected routes of administration (IV, IM, SC) Half-life (T ½) ◦ The amount of time it takes the body to metabolize/eliminate 50% of a drug ◦ E.g.
    [Show full text]
  • Is TAAR1 a Potential Therapeutic Target for Immune Dysregulation In
    Graduate Physical and Life Sciences PhD Pharmacology Abstract ID# 1081 Is TAAR1 a Potential Therapeutic Target for Immune Dysregulation in Drug Abuse? Fleischer, Lisa M; Tamashunas, Nina and Miller, Gregory M Addiction Sciences Laboratory, Northeastern University, Boston MA 02115 Abstract Discovered in 2001, Trace Amine Associated Receptor 1 (TAAR1) is a direct target of Data and Results amphetamine, methamphetamine and MDMA. It is expressed in the brain reward circuity and modulates dopamine transporter function and dopamine neuron firing rates. Newly-developed compounds that specifically target TAAR1 have recently been investigated in animal models In addition to brain, TAAR1 is expressed in immune cells METH promotes PKA and PKC Phosphorylation through TAAR1 as candidate therapeutics for methamphetamine, cocaine and alcohol abuse. These studies • We treated HEK/TAAR1 cells and HEK293 involving classic behavioral measures of drug response, as well as drug self-administration, Rhesus and Human cells with vehicle or METH, with and without strongly implicate TAAR1 as a potential therapeutic target for the treatment of addiction. In activators and inhibitors of PKA and PKC. addition to its central actions, we demonstrated that TAAR1 is upregulated in peripheral blood Cells Lines mononuclear cells (PBMC) and B cells following immune activation, and that subsequent • We performed Western blotting experiments to activation of TAAR1 by methamphetamine stimulates cAMP, similar to the function of measure levels of phospho-PKA and phospho- adenosine A2 receptors which are also present in immune cells and play a critical role in the PKC. immune response. Here, we are investigating the relationship between TAAR1 and the • We found that specific activators of PKA and adenosine A2 receptor at the level of cellular signaling and receptor dimerization.
    [Show full text]
  • MDPV Bath Salts Test
    One Step Methylenedioxypyrovalerone Drug of Abuse Test MATERIALS Analytical Sensitivity The cut-off concentration of the One Step Methylenedioxypyrovalerone Drug of Abuse Test is determined to be 1,000ng/mL. (Dip Card) Materials Provided: Test was run in 30 replicates with negative urine and standard control at ±25% cut-off and ±50% cut-off concentration levels. Test results ● Dip cards are summarized below. For Forensic Use Only ● Desiccants ● Package insert Test Result INTENDED USE Percent of Cut-off n Materials Required But Not Provided: Methylenedioxypyrovalerone Concentration in ng/mL The One Step Methylenedioxypyrovalerone Drug of Abuse Test is a lateral flow chromatographic immunoassay for the ● Specimen collection container Negative Positive qualitative detection of Methylenedioxypyrovalerone (MDPV) in human urine specimen at the cut-off level of 1,000ng/mL. This ● Disposable gloves 0% Cut-off assay is intended for forensic use only. ● Timer 30 30 0 This assay provides only a preliminary qualitative test result. A more specific confirmatory reference method, such as Liquid (No Drug Present) chromatogra -50% Cut-off phy tandem mass spectrometry (LC/MS/MS) or gas chromatography/mass spectrometry (GC/MS) must be use in INSTRUCTIONS FOR USE] 30 30 0 order to obtain a confirmed analytical result. (500ng/mL) 1) Remove the dip card from the foil pouch. -25% Cut-off 30 30 0 BACKGROUND 2) Remove the cap from the dip card. Label the device with patient or control identifications. (750ng/mL) 3) Immerse the absorbent tip into the urine sample for 5 seconds. Urine sample should not touch the plastic device. Cut-off ‘Bath salts’, a form of designer drugs, also promoted as ‘plant food’ or ‘research chemicals’, is sold mainly in head shops, on 4) Replace the cap over the absorbent tip and lay the dip card on a clean, flat, and non-absorptive surface.
    [Show full text]
  • Octopamine and Tyramine Regulate the Activity of Reproductive Visceral Muscles in the Adult Female Blood-Feeding Bug, Rhodnius Prolixus Sam Hana* and Angela B
    © 2017. Published by The Company of Biologists Ltd | Journal of Experimental Biology (2017) 220, 1830-1836 doi:10.1242/jeb.156307 RESEARCH ARTICLE Octopamine and tyramine regulate the activity of reproductive visceral muscles in the adult female blood-feeding bug, Rhodnius prolixus Sam Hana* and Angela B. Lange ABSTRACT Monastirioti et al., 1996). Octopamine and tyramine signal via The role of octopamine and tyramine in regulating spontaneous G-protein coupled receptors (GPCRs), leading to changes in second contractions of reproductive tissues was examined in the messenger levels. The recently updated receptor classification α β female Rhodnius prolixus. Octopamine decreased the amplitude of (Farooqui, 2012) divides the receptors into Oct -R, Oct -Rs β β β spontaneous contractions of the oviducts and reduced RhoprFIRFa- (Oct 1-R, Oct 2-R, Oct 3-R), TYR1-R and TYR2-R. In general, β α induced contractions in a dose-dependent manner, whereas tyramine Oct -Rs lead to elevation of cAMP while Oct -R and TYR-Rs lead to 2+ only reduced the RhoprFIRFa-induced contractions. Both octopamine an increase in Ca (Farooqui, 2012). and tyramine decreased the frequency of spontaneous bursal The movement of eggs in the reproductive system of contractions and completely abolished the contractions at Rhodnius prolixus starts at the ovaries, the site of egg maturation. 5×10−7 mol l−1 and above. Phentolamine, an octopamine receptor Upon ovulation, mature eggs are released into the oviducts antagonist, attenuated the inhibition induced by octopamine on the (Wigglesworth, 1942). Eggs are then guided, via oviductal oviducts and the bursa. Octopamine also increased the levels of peristaltic and phasic contractions, to the common oviduct, where cAMP in the oviducts, and this effect was blocked by phentolamine.
    [Show full text]
  • Comparison of the Characteristic Mass Fragmentations of Phenethylamines and Tryptamines by Electron Ionization Gas Chromatograph
    applied sciences Article Comparison of the Characteristic Mass Fragmentations of Phenethylamines and Tryptamines by Electron Ionization Gas Chromatography Mass Spectrometry, Electrospray and Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Bo-Hong Chen, Ju-Tsung Liu, Hung-Ming Chen, Wen-Xiong Chen and Cheng-Huang Lin * Department of Chemistry, National Taiwan Normal University, 88 Sec. 4 Tingchow Road, Taipei 11677, Taiwan; [email protected] (B.-H.C.); [email protected] (J.-T.L.); [email protected] (H.-M.C.); [email protected] (W.-X.C.) * Correspondence: [email protected]; Tel.: +886-2-7734-6170; Fax: +886-2-2932-4249 Received: 18 April 2018; Accepted: 19 June 2018; Published: 22 June 2018 Abstract: Characteristic mass fragmentation of 20 phenethylamine/tryptamine standards were investigated and compared by means of matrix assisted laser desorption/time-of-flight mass spectrometry (MALDI/TOFM), gas chromatography–electron ionization–mass spectrometry (GC-EI/MS) and liquid chromatography–electrospray ionization/mass spectrometry (LC-ESI/MS) + methods. As a result, three characteristic peaks ([M] and fragments from the Cβ-Cα bond breakage) were found to be unique and contained information useful in identifying 2C series compounds based on the GC-EI/MS method. We found that the protonated molecular ion ([M+H]+) and two types of fragments produced from the α-cleavage and β-cleavage processes were useful mass spectral information in the rapid screening and confirmation of phenethylamine and tryptamine derivatives when ESI/MS and MALDI/TOFMS methods were applied. This assay was successfully used to determine samples that contain illicit drugs. Keywords: phenethylamine; tryptamine; MALDI/TOFMS; GC-EI/MS; LC-ESI/MS 1.
    [Show full text]
  • Tachyphylaxis of Indirectly Acting Sympathomimetic Amines
    THE KURUME MEDICAL JOURNAL Vol. 19, No. 1, 1972 TACHYPHYLAXIS OF INDIRECTLY ACTING SYMPATHOMIMETIC AMINES II RECOVERY OF TYRAMINE TACHYPHYLAXIS AND CROSSED TACHYPHYLAXIS BETWEEN TYRAMINE AND OTHER INDI- RECTLY ACTING SYMPATHOMIMETIC AMINES IN DOGS KOICHIRO TAKASAKI, MASANOBU URABE AND RYUICHI YAMAMOTO Department of Pharmacology, Daiichi College of Pharmaceutical Sciences, Fukuoka, Japan (Received for publication September 21, 1971) The changes of blood pressure response produced by repeated adminis- tration of tyramine was investigated in morphine and pentobarbital anes- thetized and atropinized dogs. Tyramine causes gradual attenuation of the pressor effect with repeated administration of doses of 0.5 to 1 mg/kg. A definite tachyphylaxis was obtained only with repeated administration of a large dose of tyramine in total doses averaging about 60 mg/kg. The tendency to cause tachyphylaxis of tyramine was more mild than that of ephedrine-like drugs (ephedrine, methamphetamine and pheniprazine). When the pressor effect was some- what attenuated through repeated administration of tyramine, the pressor effect action of ephedrine-like drugs was slightly reduced. After the defi- nite tachyphylaxis produced by tyramine, administration of ephedrine-like drugs caused a very small or no pressor effect. Sometimes only a slight fall of blood pressure was observed. On the other hand, after tachyphylaxis due to ephedrine-like drugs, the pressor effect in response to tyramine was suppressed considerably. The attenuated pressor effect after repeated dose of tyramine was restored to some extent towards the control pressor effect after about 1 / 2 to 1 hr intervals injections or norepinephrine infusion following the last administration of tyramine. However, if some dose of ephedrine-like drugs was administered during repeated administration of tyramine, the attenuated pressor effect of tyramine was not restored after the above-mentioned intervals.
    [Show full text]
  • Effects of the Trace Amine Associated Receptor 1 Agonist RO5263397 On
    International Journal of Neuropsychopharmacology, 2015, 1–7 doi:10.1093/ijnp/pyu060 Research Article research article Effects of the Trace Amine Associated Receptor 1 Agonist RO5263397 on Abuse-Related Behavioral Indices of Methamphetamine in Rats Li Jing, PhD; Yanan Zhang, PhD; Jun-Xu Li, PhD Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY (Drs Jing and Li); Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China (Dr Jing); Research Triangle Institute, Research Triangle Park, NC (Dr Zhang). Correspondence: Jun-Xu Li, PhD, Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY ([email protected]). Abstract Background: Methamphetamine is a major drug of abuse with no effective pharmacotherapy available. Trace amine associated receptor 1 is implicated in cocaine addiction and represents a potential therapeutic target. However, the effects of trace amine associated receptor 1 agonists on addiction-related behavioral effects of methamphetamine are unknown. Methods: This study examined the effects of a trace amine associated receptor 1 agonist RO5263397 on methamphetamine- induced behavioral sensitization, methamphetamine self-administration, cue- and methamphetamine-induced reinstatement of drug seeking, and cue-induced reinstatement of sucrose-seeking behaviors in rats. Male Sprague-Dawley rats were used to examine the effects of methamphetamine alone and in combination with the trace amine associated receptor 1 agonist RO5263397 (3.2–10 mg/kg). Results: RO5263397 dose-dependently attenuated the expression of behavioral sensitization to methamphetamine, reduced methamphetamine self-administration, and decreased both cue- and a priming dose of methamphetamine-induced reinstatement of drug-seeking behaviors.
    [Show full text]
  • 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]