DOCSLIB.ORG

REVIEW ARTICLE Medical Biology 59: 21-34, 1981

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
REVIEW ARTICLE Medical Biology 59: 21-34, 1981 REVIEW ARTICLE Medical Biology 59: 21-34, 1981 ,8-CARBOLINES, PSYCHOACTIVE COMPOUNDS IN THE MAMMALIAN BODY PART I: OCCURRENCE, ORIGIN AND METABOLISM M. M. AIRAKSINEN and I. KARl FROM THE DEPARTMENT OF PHARMACOLOGYAND TOXICOLOGY, AND DEPARTMENT OF PHARMACY, UNIVERSITY OF KUOPIO, KUOPIO, FINLAND ABSTRACT We review the occurrence in nature and the formation and biotransformation in mammals of /3-car- bolines, the condensation products of tryptophan and indolealkylamines with aldehydes, with special reference to their possible role in man. They are found in many plants, some of which have been used as hallucinogens and drugs. They also occur as minor constitutients in tobacco smoke. In man tetra- hydro-p' -carboline (tetrahydronorharman), formed from tryptamine condensed with formaldehyde, oc- curs normally in plasma and is highly concentrated in platelets. The corresponding products from s-hvdroxvtrvntamlne and 5-methoxytryptamine have been identified in rats but their concentrations in man have not yet been assessed. I-Methyltetrahydro-p'-carboline (tetrahydroharman) is formed in the body as the acetaldehyde condensate after alcohol intake and its concentration is usually greatest at the time of hang-over. Its oxidation product, I-methyl-p'-carboline (harman), has also been found in human urine and platelets. Tetrahydro-/3-carbolines may be oxidized to corresponding dihydro-/3-car- bolines and f3-carbolines, at least in vitro. Due to the interesting biochemical and pharmacological effects (see part II) of .B-carbolines, several hypotheses about their role in the body can be made. The concentrations and roles of .B-carbolines in different neuropsychiatric diseases, however, remain to be determined, as suitable evaluation methods have only been developed in recent years. KEY WORDS: /I-CARBOLINES; HARMALA ALKALOIDS; TRYPTOLINES; HALLUCINOGENS;ALCOHOL; ALDEHYDES INTRODUCTION The major interest in ,8-carbolines has been prompted by the following findings: Since 1961 when McIsaac (69) reported the There is increasing evidence that some formation of ,8-carbolines in mammalian body ,8-carbohnes are normal constituents in as condensation products of indole alkyl- the human body and some are formed in amines with aldehydes, several reviews have special conditions such as after alcohol mentioned some aspects of these »natural intake (as described later in this review). hallucinogens» (3, 5, 18, 21, 25, 26, 28, 37, 39, ,8-Carbol'ines (Harm ala alkaloids) are 45, 46, 79, 91, 99); three of them appeared found in plants which have been used as while we were writing this review.,8-car- ha'llucinogens, and some pure ,8-carbolines bolines have often been described in the con- have known hallucinogenic properties (83, text of alcoholism together with tetrahydro- 84). A possible role in mental disease has isoquinolines, the corresponding condensation been suggested (70). products of catecholamines, these latter com- Tetrahydro-,8-carboline has been claimed pounds perhaps attracting most attention. to increase ethanol preference in rats (80, General interest in ,8-carbolines has, how- 81) and ,8-carbolines formed in the human ever, recently greatly increased and research body by acetaldehyde may be connected on them has consequently. intensified. The ·to alcohol dependence. Many of their ef- development of methods allowing a reliable fects in man (83) correspond to those of demonstration of the occurrence of some alcohol withdrawal. tetrahydro-,8-carbolines in human body and Some ,8-car'bolines induce tremor and har- some recent receptor studies has opened up maline has been used to produce experi- new aspects of their role and mode of action. mental tremor (33, 66, 94, 108, 123). 22 M. M. Airaksinen and I. Kari R'~COOH1 --;. R'~COOH1 --? R'lOt;YCOOHI - -.,. R'0lOI;VCOOH1 N NH2 RCHO N NH N ~N N ~NH H HR HR HR IA ][A mA I I I ~ ~ ~ R~ ---.;.R~ __.,.R'~I R' Vr\i3!J NH2 RCHO ~~>-y-'NH V'N;>'l --~'OrH H HR HR HR IB /-11 ][B mB / RCO~ / 'i' / I R' I ~H~N)J ~ H c=o I c R Fig. 1. Possible routes of mammalian synthesis of tetrahydro-,s'-carbolines (THBCs, I), dihydro-ji- carbolines (DHBCs, II) and ji'-carbolines (BCs, III).R' = H, OH or OCH3; R = H, CHR (or other radi- cal). The dotted arrows indicate more uncertain routes. - Some tB-carbolines are competitive inhi'bi- the literature. tB-Carboline (Fig. 1, III B; R = tors of the saturable sodium transport and R' = H) itself is usually known as norhar- harmaline has 'been used in studies of mane and I-methyl-tB-carboline (III B; R = sodium-dependent transport of amino CH~,R' = H) as harmane (with or without an acids etc.(105). e on the end). The primary condensation pro- tB-Carholines inhibrt monoamine oxidase ducts of indole-ethylamines, however, are (MAO) (38, 42), particularly A-type (19, 85), 1,2,3,4-tetrahydro-~-carbolines (THBCs) (Fig. and 'have 'been used as short acting MAO 1, I) or 2,3,4,9-tetrahydro-1H-pyrido[3,4-bJin- inhibitors. doles or 1,2,3,4-tetrahydronorharmane deriva- Some tetrahydro-zi-carbolines effectively tives, also named tryptolines by the Barchas' inhibitthe uptake of 5-hydroxytryptamine group (9). These as well as (1,2- 'Or) 3,4-di- (5-HT)(8, 53) and increase 5-HT concen- hydro-ji-carbobines, 4,9-dihydl'o-3H-pyrido- tration in the brain (72) and they have [3,4..;bJindolesor dihydronorharmanes (Fig. 1, sometimes been used experimentally as II)(the probable site of the double bond is serotonergic drugs. 1,2 but it has not often been determined) Effective binding of some ~-carbolines to may be oxidized (aromatized) to tB-carbolines benzadiazepine receptors has recently at least in vitro, perhaps also in vivo. been shown (6, 16, 31, 94) and they have Different numbering systems for the atoms been suggested as the natural ligands of in ~-carbolines have been used and even the »benzodiazepine» receptors, Binding to present most official numbering system dif- opiate receptors has also been described fers from that used in tryptamines (Fig. 1). (6). Thus, for example, the tryptamine 5-position Some tB-carbolines occurring in tobacco is 6-position .in ~-carbolines. The »tryptoIine» smoke and pyrolysis products of proteins naming of tetrahydro-ri-carbolines, however, in food are comutagenic (115, 116) and may uses principally the same numbering as for have carcinogenic or cocarcinogenic pro- tryptamines.Even editors of some scientific perties. journals 'have ,been confused because, for instance, 6-methoxy-tetrahydro-tB-carbohne St1"uctu1"es and nomenclatu1"e is the same as 5-methoxytryptoline. Here we ~-Carbolines or 2-carbolines is the often re- wil'l use the tB-carboline nomenclature and commended name for i9H-pyrido[3,4-bJindo- their usual numbering system. The term ~- les, but Chemical Abstracts uses the latter carbo lines refers .to the group which also in- names and a jungle of 'Other names occurs in cludes dihydro-ri-carbolines (DHBCs) and (J-Ca1'bolines in the mammalian body 23 tetrahydro-zi-carbolines (TRBCs) or to the plants seem to make mainly nonsaturated »fully aromatized» derivatives (BCs) of the BCs and DRBCs, but some, e.g. Elaeagnus specific compound p-carboline (BC). The niger L., also TRBCs. Some plants produce shortening Be is used only for the latter several p-carbolines, some are rather specific. meaning. Although the tryptol:ine naming is After a feeding of Passiflora edulis with [14C]- shorter and logical it has only been made tryptophan nearly all the radioactivity found for tetrahydro-zi-carbolines. The names ori- was in [14C]-harman (22). ginally given to the plant alkaloids or those Some other alkaloids with larger molecules derived from harman and other Harrnala al- contain a fJ-cal"boline ring system as part of kaloids are probably the 'best known but less a complicated skeleton. The effects of these logical. alkaloids usually differ from those of simple fJ-carbolines. The Rauwolfia alkaloids may be the best known representatives of such P-CARBOLINES IN PLANTS compounds, which are not dealt with in this The people living in various parts of South review. Ho (39) has reviewed the effects of America, Asia and Africa have known for yohimbine in the context of p-carbolines. thousands of years the potent psychoactivity p-Carbolines in food and tobacco of several plants containing p-carbolines (63, 84). Ancient Greeks and also Europeans of Aromatic p-carbolines, BC (norharman) and our centuries used Peganum tuirmaia L. 1-Me-BC(harman) have been described as among others in a »truth serum» (56). In being formed as pyrolysis products of trypto- India it had been used in religious ceremonies phan and proteins (55, 115, 116) which have (27, 63). West American natives have used been identified in cigarette smoke (90) and extracts from Passiiiora species (edulis and in the surface of charred meat and fish (82). incarnata) for several indications e.g. insom- The concentration of p-carbolines was con- nia, spasms and cramps (63). A drink called siderable if the surface was dark brown but ayahuasca, caapi, natema, pinde or yaje and very small if the meat remained only light made from the South American liane Banis- brown. teriopsis caapi, Spr. ex Griseb. (named Banis- teria caapi by Spruce) and preparations from /:i-CARBOLINES IN MAMMALS some other plants of the Malpighiaceae have INCLUDING MAN been used by Indians as narcotic and hallu- cinogenic agents in religious rituals (2, 44, 84, As shown later in this paper, TRBCs are 102, 103, 113) and sometimes also in other easily formed in vitro in various mammalian situations e.g. »to see the future» before tissues. Consequently many investigators have selecting a wife. Even habituation may have presented hypotheses about the possible form- occurred (61). Moreover, the anthelmintic ef- ation of p-carbolines in vivo.Until now nine fect of some plants containing p-carbolines p-carboline derivatives have been reported has been known to the natives for centuries to occur in various mammalian tissues and (24).
Load more

Recommended publications
  • Contribution of Individual P450 Isozymes to the O-Demethylation of The
    JPET Fast Forward. Published on January 21, 2003 as DOI: 10.1124/jpet.102.047050 JPET FastThis articleForward. has not Published been copyedited on and January formatted. 21,The final2003 version as DOI:10.1124/jpet.102.047050 may differ from this version. JPET/2002/47050 Contribution of individual P450 isozymes to the O-demethylation of the psychotropic β-carboline alkaloids harmaline and harmine Downloaded from u 1 Ai-Ming Y , Jeffrey R. Idle , Kristopher W. Krausz, Adrian Küpfer and Frank J. jpet.aspetjournals.org Gonzalez* Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, at ASPET Journals on September 28, 2021 Bethesda, MD 20892, USA (A.M.Y., K.W.K, F.J.G.) Department of Clinical Pharmacology, University of Bern, Murtenstraße 35, CH-3010 Bern, Switzerland (J.R.I., A.K.) 1 Copyright 2003 by the American Society for Pharmacology and Experimental Therapeutics. JPET Fast Forward. Published on January 21, 2003 as DOI: 10.1124/jpet.102.047050 This article has not been copyedited and formatted. The final version may differ from this version. JPET/2002/47050 Running title: Metabolism of harmaline and harmine Address Correspondence to: Dr. Frank J. Gonzalez Laboratory of Metabolism National Cancer Institute National Institutes of Health Bldg. 37, Rm. 2A19A Downloaded from Bethesda, MD 20892, USA Phone: 301-496-9067 Fax: 301-496-8419 jpet.aspetjournals.org E-mail: [email protected] Text pages: 25 Tables: 4 at ASPET Journals on September 28, 2021 Figures: 7 References: 53 Words in: Abstract: 238 Introduction: 636 Discussion: 1277 Abbreviations used: CNS, central nervous system; CYP, cytochrome P450; HLM, human liver microsomes; MLM, mouse liver microsomes; HPLC, high performance liquid chromatography; LC-MS/MS, liquid chromatography tandem mass spectrometry; 5- HT, 5-hydroxytryptamine; MPTP, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
    [Show full text]
  • Effects of Smoking and Gender on Tetrahydroisoquinolines and Beta-Carbolines in a Healthy Population and During Alcohol Detoxification
    Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2008 Effects of Smoking and Gender on Tetrahydroisoquinolines and Beta-Carbolines in a Healthy Population and During Alcohol Detoxification Satjit Singh Brar Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Pharmacy and Pharmaceutical Sciences Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/902 This Dissertation 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]. © Satjit Singh Brar 2008 All Rights Reserved EFFECTS OF SMOKING AND GENDER ON TETRAHYDROISOQUINOLINES AND β–CARBOLINES IN A HEALTHY POPULATION AND DURING ALCOHOL DETOXIFICATION A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. by SATJIT SINGH BRAR B.S., University of California at Santa Barbara, 1998 Director: Jürgen Venitz, MD, Ph.D. Associate Professor, Department of Pharmaceutics Virginia Commonwealth University Richmond, Virginia May 2008 ii Acknowledgements Jürgen Venitz, first and foremost, for giving me the opportunity to pursue graduate studies under his guidance. His mentoring in academics and research has been truly motivating and inspirational. Members of my graduate committee, Drs. Jürgen Venitz, John Rosecrans, Patricia Slattum, Vijay Ramchandani, H. Thomas Karnes, and Hee-Yong Kim for their efforts, patience and time for serving on my committee. Patricia Slattum for her advice and encouragement. She has provided valuable aid over the years by giving guidance throughout my tenure in the Pharm.D./Ph.D.
    [Show full text]
  • Pharmacological and Therapeutic Effects of Peganum Harmala and Its Main Alkaloids
    PHCOG REV. PLANT REVIEW Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids Milad Moloudizargari, Peyman Mikaili1, Shahin Aghajanshakeri, Mohammad Hossein Asghari, Jalal Shayegh2 Student of Veterinary Medicine, Faculty of Veterinary Medicine, Urmia University, 1Department of Pharmacology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, 2Veterinary Medicine, Faculty of Agriculture and Veterinary, Shabestar Branch, Islamic Azad University, Shabestar, Iran Submitted: 24-12-2012 Revised: 28-12-2012 Published: **-**-**** ABSTRACT Wild Syrian rue (Peganum harmala L. family Zygophyllaceae) is well‑known in Iran and various parts of this plant including, its seeds, bark, and root have been used as folk medicine. Recent years of research has demonstrated different pharmacological and therapeutic effects of P. harmala and its active alkaloids, especially harmine and harmaline. Analytical studies on the chemical composition of the plant show that the most important constituents of this plant are beta‑carboline alkaloids such as harmalol, harmaline, and harmine. Harmine is the most studied among these naturally occurring alkaloids. In addition to P. harmala (Syrian rue), these beta-carbolines are present in many other plants such as Banisteria caapi and are used for the treatment of different diseases. This article reviews the traditional uses and pharmacological effects of total extract and individual active alkaloids of P. harmala (Syrian rue). Key words: Harmine, harmaline, peganum harmala, pharmacological effects, wild syrian rue INTRODUCTION including its seeds, fruits, root, and bark, have been used as folk medicine for a long time in Iran and other countries [Table 1]. Harmal[1] (Peganum harmala L. family Zygophyllaceae) is a Many pharmacological surveys have shown different effects of perennial, glabrous plant which grows spontaneously in P.
    [Show full text]
  • Tacrine, Trolox and Tryptoline As Lead Compounds for The
    Tacrine, trolox and tryptoline as lead compounds for the design and synthesis of multi-target drugs for Alzheimer’s disease therapy. by Gerard A. Kenfack Teponnou Tacrine, trolox and tryptoline as lead compounds for the design and synthesis of multi-target drugs for Alzheimer’s disease therapy. Gerard A. Kenfack Teponnou A dissertation submitted in partial fulfilment of the requirements for the degree MASTER IN PHARTMACEUTICAL CHEMISTRY. Supervisor: Prof Sarel F. Malan Co-supervisor: Prof J. Joubert April 2016 PHARMACEUTICAL CHEMISTRY, SCHOOL OF PHARMACY, UNIVERSITY OF THE WESTERN CAPE, PRIVATE BAG X17, BELLVILLE, 7535. Dedicated to my late grandmothers, Makougou Christine, my late aunt’s husband, Tiegoh Jean de Dieu and my late brothers and sisters: Makeugue Alliance Belise, Yougang Pascal, Tchebonssou Celine and Kenfack Raymon. KEYWORDS Alzheimer’s disease Amyloid Beta Cholinesterases Molecular docking Multifactorial disease Multifunctional drugs Multi-target directed ligand Reactive oxygen species Tacrine Trolox Tryptoline i DECLARATION I declare that “Tacrine, trolox and tryptoline as lead compounds for the design and synthesis of multi-target drugs for Alzheimer’s disease therapy” is my own work and that it has not been submitted for any other degree or examination at any other university, and that all the sources I have used or quoted have been indicated and acknowledged by complete reference. Full name researcher…………………………………………………………….. Date………………………………………. ii ABSTRACT The cascade of neurotoxic events involved in the pathogenesis of Alzheimer’s disease may explain the inefficacy of currently available treatment based on acetylcholinesterase inhibitors (AChEI - donepezil, galantamine, rivastigmine) and N-methyl-D-aspartate (NMDA) antagonists (memantine). These drugs were designed based on the “one-molecule- one-target” paradigm and only address a single target.
    [Show full text]
  • Chemistry for Pharmacy Students : General, Organic
    Chemistry for Pharmacy Students General, Organic and Natural Product Chemistry Satyajit D. Sarker University of Ulster, Coleraine, Northern Ireland, UK Lutfun Nahar University of Ulster, Coleraine, Northern Ireland, UK Chemistry for Pharmacy Students Chemistry for Pharmacy Students General, Organic and Natural Product Chemistry Satyajit D. Sarker University of Ulster, Coleraine, Northern Ireland, UK Lutfun Nahar University of Ulster, Coleraine, Northern Ireland, UK Copyright #2007 John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England Telephone (þ44) 1243 779777 Email (for orders and customer service enquiries): [email protected] Visit our Home Page on www.wiley.com All Rights Reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning or otherwise, except under the terms of the Copyright, Designs and Patents Act 1988 or under the terms of a licence issued by the Copyright Licensing Agency Ltd, 90 Tottenham Court Road, London W1T 4LP, UK, without the permission in writing of the Publisher. Requests to the Publisher should be addressed to the Permissions Department, John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England, or emailed to [email protected], or faxed to (þ44) 1243 770620. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The Publisher is not associated with any product or vendor mentioned in this book.
    [Show full text]
  • Pharmacological Importance of Optically Active Tetrahydro-Β-Carbolines and Synthetic Approaches to Create the C1 Stereocenter
    Molecules 2014, 19, 1544-1567; doi:10.3390/molecules19021544 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Pharmacological Importance of Optically Active Tetrahydro-β-carbolines and Synthetic Approaches to Create the C1 Stereocenter Aino E. Laine, Christopher Lood and Ari M. P. Koskinen * Laboratory of Organic Chemistry, Department of Chemistry, School of Chemical Tehcnology, Aalto University, PO Box 16100, Kemistintie 1, Aalto FI-00076, Finland; E-Mails: [email protected] (A.E.L.); [email protected] (C.L.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +358-50-555-3310. Received: 19 December 2013; in revised form: 17 January 2014 / Accepted: 20 January 2014 / Published: 27 January 2014 Abstract: 1,2,3,4-Tetrahydro-β-carbolines (THβCs) are a pharmacologically important group of compounds belonging to the indole alkaloids. C1-Substituted optically active THβCs have been the target of extensive synthetic efforts due to the presence of the scaffold in numerous natural products and synthetic targets. This review briefly summarizes the methods to obtain the C1 stereocenter and concentrates on evaluating the pharmacological importance of optically active C1-substituted THβCs, including their PDE5-inhibitory, antimalarial, antiviral and antitumor activities. Keywords: tetrahydro-β-carboline; THβC; pharmacological importance; biological activity; C1-substituted THβC 1. Introduction 1,2,3,4-Tetrahydro-β-carbolines (THβCs), a compound class within the indole alkaloids, consist of a variety of both simple and complex natural and synthetic compounds [1]. These compounds possess a vast spectrum of biological activities and their use in novel pharmacological applications is under constant study, as the THβC structure is present in drugs currently available on the market, drug candidates under development and many other pharmacologically interesting compounds [2–17].
    [Show full text]
  • Fragment-Based Approaches in GPCR-Targeted Drug Discovery Thesis
    Fragment-based approaches in GPCR-targeted drug discovery Thesis Ádám Andor Kelemen PhD candidate György Miklós Keserű DSc, FRSC supervisor Medicinal Chemistry Research Group Research Centre for Natural Sciences Hungarian Academy of Sciences Budapest 2018 Table of contents Table of contents ................................................................................................ 2 List of abbreviations .......................................................................................... 7 Acknowledgements ......................................................................................... 10 Chapter 1 – Introduction ................................................................................ 11 1.1. Fragment-based drug discovery ........................................................ 11 1.1.1. Concept of Fragment-based drug discovery ............................. 11 1.1.2. Strategies and examples ............................................................... 12 1.1.2.1. Fragment-based drug design workflow .................................. 12 1.1.2.2. Fragment optimization strategies............................................. 13 1.2. G-Protein Coupled Receptors ............................................................. 14 1.2.1. Signalization and classification ................................................... 14 1.2.2. X-Ray crystal structures of aminergic GPCR’s .......................... 19 1.3. Medicinal Chemistry of Serotonin (5-HT) receptor ligands ........... 21 1.3.1. Serotonin Receptor Subtype 6 (5-HT6R)64
    [Show full text]
  • Autoradiographic Localization of Tryptamine Binding Sites in the Rat and Dog Central Nervous System
    The Journal of Neuroscience January 1986, 6(l): !+I-101 Autoradiographic Localization of Tryptamine Binding Sites in the Rat and Dog Central Nervous System James K. McCormack, Alvin J. Beitz, and Alice A. Larson Department of Veterinary Biology, University of Minnesota, St. Paul, Minnesota 55108 Tryptamine, an endogenous trace amine, is currently postulated posing evidence for such a role has been reviewed by Jones to be a neuromodulator or neurotransmitter in the mammalian (1982). CNS. High-affinity binding sites have been described for trypt- More recently, additional supporting evidence that docu- amine in rat brain homogenate preparations. The present study ments a high-affinity binding site for H3-tryptamine in rat brain further characterizes tryptamine binding throughout the CNS homogenateshas been presented(Cascio and Kellar, 1982; Kel- and delineates its distribution using in viiro receptor binding in lar and Cascio, 1982). Since then, other investigators have also conjunction with autoradiographic techniques. Saturation stud- demonstrated that tryptamine binding sites are present in the ies on ZO-pm-thick brain sections suggest a single class of bind- CNS and are distinct from those of serotonin binding sites ing sites (Hill coefficient = 0.97 + 0.04) with a high affinity (Rommelspacher and Kaufmann, 1983; Wood et al., 1984). (K, = 4.79 f 1.55 nM). In competition studies, kynuramine and Tryptamine binding has been found to be strongly inhibited by tetrahydrobetacarboline significantly inhibited HI-tryptamine beta-carbolines(Cascio and Kellar, 1983; Rommelspacherand binding while serotonin, dopamine, and phenylethylamine failed Kaufmann, 1983; Wood et al., 1984), kynuramine (Charlton et to significantly inhibit it. The most potent inhibitor of H3-trypt- al., 1984), and derivatives of phenylethylamine (PEA) (Cascio amine binding was tryptamine (K, = 4.19 f 2.13 nM).
    [Show full text]
  • Alkaloids.Tarek Kakhia.Pdf
    ADANA UNIVERSTY – INDUSTRY JOINT RESEARCH CENTER ALKALOIDS & ALKALOIDS PLANTS By TAREK ISMAIL KAKHIA 1 2 INDEX Itam Page Itam No 1 - Alkaloids : 1 Alkaloids 2 Atropine 3 Caffeine 4 Cocaine 5 Codaine 6 Heroine 7 Lidocaine 8 Morphin 9 Nicotine 10 Papaverine 11 Solanine 2 - Alkaliod Plants 1 Belladonna 2 Cannabis 3 Cannabis ( Drug ) 4 Cannabis ( Altivation ) 5 Coca 6 Coffee 7 Datura Stramonium 8 Datura 9 Hashish 10 Khat 11 Opium 12 Opium Poppy 3 13 Tea 14 Tobacco 15 Yerba Mate 3 - Alkaliod Plants Time Line 1 Time Line of Cannabis 1 2 Time Line of Cannabis 2 3 Time Line of Coca 4 Time Line of Coffee 5 Time Line of Datura 6 Time Line of Hashish 7 Time Line of Khat 8 Time Line of Poppy & Opium 9 Time Line of Tea 10 Time Line of Tobacco 11 Time Line of Yerba Mat 12 Time Line of 4 - Extension and Supplements 1 Night Shade Alkaloid Toxins Atropine , Scopolamine and Solanine 2 Hyoscyamus Niger 3 Nerium Oleander 4 PART – 1 ALKALOIDS 5 6 Alkaloid Chemical structure of ephedrine, a phenethylamine alkaloid Contents : 1 Introduction 2 Alkaloid Classifications 3 Physicochemical Properties 4 Category : Alkaloids 1 – Introduction : Alkaloids are naturally occurring chemical compounds containing basic nitrogen atoms . The name derives from the word alkaline and was used to describe any nitrogen - containing base. Alkaloids are produced by a large variety of organisms, including bacteria, fungi, plants, and animals and are part of the group of natural products (also called secondary metabolites ) . Many alkaloids can be purified from crude extracts by acid - base extraction.
    [Show full text]
  • Review CYP2D in the Brain
    p337 p.1 [100%] Drug Metab. Pharmacokin. 18 (6): 337–349 (2003). Review CYP2D in the Brain Yoshihiko FUNAE, Wataru KISHIMOTO,ToshioCHO, Toshiro NIWA, and Toyoko HIROI Department of Chemical Biology, Osaka City University, Medical School, Osaka, Japan Summary: CYP2D1, 2D2, 2D3, and 2D4 are major CYP2D isoforms expressed in the rat. In humans, only CYP2D6 is expressed. In rat brain, the mRNA for CYP2D4 is most abundant in cerebellum, striatum, pons and medulla oblongata. In human brain, CYP2D6 mRNA expression was detected in all regions with highest levels observed in cerebellum. CYP2D isoforms are involved in the metabolism of not only xenobiotics such as antidepressants, b-adrenergic blockers, antiarrhysthmics, and antihypertensives, but also endogenous compounds such as trace amine and neurosteroids. Among 11 isoforms of human recombinant P450s, only CYP2D6 exhibit- ed an ability to e‹ciently convert tyramine which exists in the brain, to dopamine. CYP2D4 and CYP2D6 which are the predominant CYP2D isoforms in the rat and human brain, respectively, possess 21-hydroxylation activity for both progesterone and allopregnanolone. CYP2D4, not P450c21, works as a steroid 21-hydroxylase in the brain. These results suggested that CYP2D in the brain may be involved in the metabolism of neuronal amines and steroids and in the regulation of the central nervous system. Key words: CYP2D; CYP2D4; CYP2D6; brain; dopamine formation; steroid 21-hydroxylation system or on the heart. It is thus of immense interest Introduction whether CYP2D6 is not only localized in the liver,8) but Six genes, named CYP2D1 through CYP2D5 and also found at high levels in these two target tissues, the CYP2D18,werefoundintherat.1–3) CYP2D1 catalyzes brain9,10) and heart.11) a debrisoquine 4-hydroxylase and exhibits a closest The polymorphic hydroxylation of debrisoquine was enzymatic relationship to human CYP2D6.
    [Show full text]
  • The University of Chicago Engineering Halogenases
    THE UNIVERSITY OF CHICAGO ENGINEERING HALOGENASES FOR SELECTIVE FUNCTIONALIZATION OF BIOACTIVE MOLECULES A DISSERTATION SUBMITTED TO THE FACULTY OF THE DIVISION OF THE PHYSICAL SCIENCES IN CANDIDACY FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF CHEMISTRY BY JAMES T. PAYNE CHICAGO, ILLINOIS DECEMBER 2015 To my wife Dana to offer you a fraction of my gratitude for your enduring love and support. TABLE OF CONTENTS LIST OF TABLES ……………………………………………………………………….. v LIST OF FIGURES ……………………………………………………………………… vi LIST OF SCHEMES …………………………………………………………………….. x ACKNOWLEDGEMENTS ……………………………………………………………… xi ABSTRACT ……………………………………………………………………………… xiii PREFACE ………………………………………………………………………………... xvi CHAPTER ONE An Introduction to Halogenases and Directed Evolution …………………….. 1 1.1 The Importance of Site-Selective Halogenation …………………………………. 1 1.2 An Introduction to Halogenases …………………………………………………. 5 1.2.1 SAM Dependent Halogenases ……………………………………………. 6 1.2.2 Haloperoxidases ………………………………………………………….. 10 1.2.3 α-Ketoglutarate Dependent Halogenases (ADHs) ……………………….. 11 1.2.4 Flavin Dependent Halogenases (FDHs) ………………………………….. 15 1.3 The Use of Directed Evolution to Engineer Enzymes ………………………….... 20 1.4 Conclusions ………………………………………………………………………. 29 1.5 References ………………………………………………………………………... 30 CHAPTER TWO Enhancing the Expression of Wild-Type RebH and an Exploration of Its Substrate Scope …………………………………………………………………. 34 2.1 Introduction ………………………………………………………………………. 34 2.2 Results and Discussion …………………………………………………………… 37 2.2.1 The Selection of a Suitable
    [Show full text]
  • Views', See Rahwan, 1974; Rahwan, 1975)
    INFORMATION TO USERS This was produced from a copy of a document sent to us for microfilming. While the most advanced technological means to photograph and reproduce this document have been used, the quality is heavily dependent upon the quality of the material submitted. The following explanation of techniques is provided to help you understand markings or notations which may appear on this reproduction. 1.The sign or “target” for pages apparently lacking from the document photographed is “Missing Page(s)”. If it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting through an image and duplicating adjacent pages to assure you of complete continuity. 2. When an image on the film is obliterated with a round black mark it is an indication that the film inspector noticed either blurred copy because of movement during exposure, or duplicate copy. Unless we meant to delete copyrighted materials that should not have been filmed, you will find a good image of the page in the adjacent frame. 3. When a map, drawing or chart, etc., is part of the material being photo­ graphed the photographer has followed a definite method in “sectioning” the material. It is customary to begin filming at the upper left hand comer of a large sheet and to continue from left to right in equal sections with small overlaps. If necessary, sectioning is continued again—beginning below the first row and continuing on until complete. 4. For any illustrations that cannot be reproduced satisfactorily by xerography, photographic prints can be purchased at additional cost and tipped into your xerographic copy.
    [Show full text]