A COMPARISON Oit SOME UI TEE Being
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Determination of Sex 43, Elm Park Gardens, THOSE Who Are Interested in the Heredity of Sex Chelsea, S.W.Lo
APRIL 14, 1934 NATURE 579 sa was correctly computed in five minutes, 510 in genes outweigh the female and the result is the twenty seconds and 610 in seventy seconds. normal haplo-X male." Division was a slower process and 9 digits divided Thus, as my italics show, the experimental by 3 took times varying from two and a half to geneticist seems to agree with what Prof. MacBride seven and three quarters minutes. has expressed in more generally intelligible language ; Square roots of 6 digit numbers were extracted in not only in admitting the essential sameness of sex less than a minute while cube roots took longer. in all organisms but also in understanding the Curiously enough, the memorising of a number of function of proportion in its determination in some 27 digits was not done successfully, although he of them. Unanimity among the different branches of could repeat questions which had been put to him biology has therefore been reached after a long period and their answers after some days had elapsed, and of divergence, from entirely different data and, what would break off calculations in the middle to ask for is more, apparently unawares. Such an event, surely, milk or cigarettes, taking up the calculations again should not be allowed to pass without notice and where he had broken off. His methods of working without applause. The usual view that the chromo were not discovered, but he had obviously memorised some theory of sex determination criticised by the squares of two digit numbers, and less completely MacBride was a special hypothesis put forward by the products of two digit numbers. -
Headshop Highs & Lows
HeadshopHeadshop HighsHighs && LowsLows AA PresentationPresentation byby DrDr DesDes CorriganCorrigan HeadshopsHeadshops A.K.A.A.K.A. ““SmartSmart ShopsShops””,, ““HempHemp ShopsShops””,, ““HemporiaHemporia”” oror ““GrowshopsGrowshops”” RetailRetail oror OnlineOnline OutletsOutlets sellingselling PsychoactivePsychoactive Plants,Plants, ‘‘LegalLegal’’ && ““HerbalHerbal”” HighsHighs asas wellwell asas DrugDrug ParaphernaliaParaphernalia includingincluding CannabisCannabis growinggrowing equipment.equipment. Headshops supply Cannabis Paraphernalia HeadshopsHeadshops && SkunkSkunk--typetype (( HighHigh Strength)Strength) CannabisCannabis 1.1. SaleSale ofof SkunkSkunk--typetype seedsseeds 2.2. AdviceAdvice onon SinsemillaSinsemilla TechniqueTechnique 3.3. SaleSale ofof HydroponicsHydroponics && IntenseIntense LightingLighting .. CannabisCannabis PotencyPotency expressedexpressed asas %% THCTHC ContentContent ¾¾ IrelandIreland ¾¾ HerbHerb 6%6% HashHash 4%4% ¾¾ UKUK ¾¾ HerbHerb** 1212--18%18% HashHash 3.4%3.4% ¾¾ NetherlandsNetherlands ¾¾ HerbHerb** 20%20% HashHash 37%37% * Skunk-type SkunkSkunk--TypeType CannabisCannabis && PsychosisPsychosis ¾¾ComparedCompared toto HashHash smokingsmoking controlscontrols ¾¾ SkunkSkunk useuse -- 77 xx riskrisk ¾¾ DailyDaily SkunkSkunk useuse -- 1212 xx riskrisk ¾¾ DiDi FortiForti etet alal .. Br.Br. J.J. PsychiatryPsychiatry 20092009 CannabinoidsCannabinoids ¾¾ PhytoCannabinoidsPhytoCannabinoids-- onlyonly inin CannabisCannabis plantsplants ¾¾ EndocannabinoidsEndocannabinoids –– naturallynaturally occurringoccurring -
Ergot Alkaloids As Dopamine Agonists: Comparison in Two Rodent Models
European Journal of Pharmacology, 37 (1976) 295-302 295 © North-Holland Publishing Company, Amsterdam - Printed in The Netherlands ERGOT ALKALOIDS AS DOPAMINE AGONISTS: COMPARISON IN TWO RODENT MODELS GILL ANLEZARK, CHRIS PYCOCK and BRIAN MELDRUM Department of Neurology, Institute of Psychiatry, Denmark Hill, London, SE5 8AF, U.K. Received 18 December 1975, revised MS received 20 February 1976, accepted 26 February 1976 G. ANLEZARK, C. PYCOCK and B. MELDRUM, Ergot alkaloids as dopamine agonists: comparison in two rodent models, European J. Pharmacol. 37 (1976) 295-302. A series of ergot alkaloids, together with the DA agonists apomorphine and piribedil, were tested for protec- tive effects against audiogenic seizures in an inbred strain of mice (DBA/2) and for induction of circling behaviour in mice with unilateral destruction of one nigrostriatal DA pathway. The order of potency against audiogenic sei- zures was apomorphine> ergocornine> bromocryptine > ergometrine> LSD> methysergide > piribedil while that observed in the rotating mouse model was apomorphine> ergometrine> ergocornine> brornocryptine > piribedil. LSD caused only weak circling behaviour even when administered in high doses (> 1 mg/kg). Methyser- gide was ineffective. Prior administration of the neuroleptic agent haloperidol blocked the effect of DA agonists and of ergot alkaloids in both animal models. The possible action of ergot alkaloids as DA agonists is discussed. Ergot alkaloids Audiogenic seizures Dopamine agonists Circling behaviour 1. Introduction gic synapses, in two rodent pharmacological models. The first model studied is 'audiogen- The pharmacology of the ergot alkaloids is ic' seizures in genetically susceptible mice. complex and not well understood. Peripheral- The severity of the seizure responses to audi- ly, they act on smooth muscle as 5-hydroxy- tory stimulation can be modified by a variety tryptamine (5-HT) antagonists (Goodman and of drugs believed to act on monoaminergic Gilman, 1971) and as a-adrenergic blockers transmission in the brain (Lehmann, 1970). -
WO 2010/099522 Al
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 2 September 2010 (02.09.2010) WO 2010/099522 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 45/06 (2006.01) A61K 31/4164 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/4045 (2006.01) A61K 31/00 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US2010/025725 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 1 March 2010 (01 .03.2010) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, (26) Publication Language: English TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/156,129 27 February 2009 (27.02.2009) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (71) Applicant (for all designated States except US): ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, HELSINN THERAPEUTICS (U.S.), INC. -
Risk Assessment of Argyreia Nervosa
Risk assessment of Argyreia nervosa RIVM letter report 2019-0210 W. Chen | L. de Wit-Bos Risk assessment of Argyreia nervosa RIVM letter report 2019-0210 W. Chen | L. de Wit-Bos RIVM letter report 2019-0210 Colophon © RIVM 2020 Parts of this publication may be reproduced, provided acknowledgement is given to the: National Institute for Public Health and the Environment, and the title and year of publication are cited. DOI 10.21945/RIVM-2019-0210 W. Chen (author), RIVM L. de Wit-Bos (author), RIVM Contact: Lianne de Wit Department of Food Safety (VVH) [email protected] This investigation was performed by order of NVWA, within the framework of 9.4.46 Published by: National Institute for Public Health and the Environment, RIVM P.O. Box1 | 3720 BA Bilthoven The Netherlands www.rivm.nl/en Page 2 of 42 RIVM letter report 2019-0210 Synopsis Risk assessment of Argyreia nervosa In the Netherlands, seeds from the plant Hawaiian Baby Woodrose (Argyreia nervosa) are being sold as a so-called ‘legal high’ in smart shops and by internet retailers. The use of these seeds is unsafe. They can cause hallucinogenic effects, nausea, vomiting, elevated heart rate, elevated blood pressure, (severe) fatigue and lethargy. These health effects can occur even when the seeds are consumed at the recommended dose. This is the conclusion of a risk assessment performed by RIVM. Hawaiian Baby Woodrose seeds are sold as raw seeds or in capsules. The raw seeds can be eaten as such, or after being crushed and dissolved in liquid (generally hot water). -
Hallucinogens: an Update
National Institute on Drug Abuse RESEARCH MONOGRAPH SERIES Hallucinogens: An Update 146 U.S. Department of Health and Human Services • Public Health Service • National Institutes of Health Hallucinogens: An Update Editors: Geraline C. Lin, Ph.D. National Institute on Drug Abuse Richard A. Glennon, Ph.D. Virginia Commonwealth University NIDA Research Monograph 146 1994 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 ACKNOWLEDGEMENT This monograph is based on the papers from a technical review on “Hallucinogens: An Update” held on July 13-14, 1992. The review meeting was sponsored by the National Institute on Drug Abuse. COPYRIGHT STATUS The National Institute on Drug Abuse has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required. All other material in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors. Citation of the source is appreciated. Opinions expressed in this volume are those of the authors and do not necessarily reflect the opinions or official policy of the National Institute on Drug Abuse or any other part of the U.S. Department of Health and Human Services. The U.S. Government does not endorse or favor any specific commercial product or company. -
Update of the Generic Definition for Tryptamines
ACMD Advisory Council on the Misuse of Drugs Chair: Professor Les Iversen Secretary: Zahi Sulaiman 2nd Floor (NW), Seacole Building 2 Marsham Street London SW1P 4DF Tel: 020 7035 1121 [email protected] Norman Baker MP, Minister for Crime Prevention Home Office 2 Marsham Street London SW1P 4DF 10 June 2014 Dear Minister, In December 2013, you commissioned the ACMD to begin a regular review of generic definitions under the Misuse of Drugs Act 1971, with the aim of capturing emerging new psychoactive substances. These drugs are variants of controlled drugs and fall outside the existing scope of the Misuse of Drugs Act 1971. The ACMD has considered evidence available on tryptamines in the context of the Misuse of Drugs Act 1971 and I enclose the Advisory Council’s advice and an expanded definition for tryptamine compounds with this letter. The ACMD’s NPS Committee has firstly reviewed previous research and existing controls to identify those tryptamines now seen to evade the existing controls. The ACMD has also reviewed data provided by the Home Office’s early warning systems and networks, clinical toxicology, prevalence and neuropharmacology in arriving at the expanded generic definition. This expanded generic definition will bring drugs such as alpha-methyltryptamine (AMT) as well as 5-MeO-DALT within the scope of the Misuse of Drugs Act 1971. These are highly potent hallucinogens which act on the 5HT2A receptor, in the same way as LSD. The ACMD therefore recommends that the tryptamines covered by the proposed expanded generic definition in this report, are controlled under the Misuse of Drugs Act (1971) as Class A substances. -
Package Leaflet: Information for the Patient Dostinex® 0.5 Mg Tablets
Package leaflet: Information for the patient Dostinex® 0.5 mg Tablets cabergoline Read all of this leaflet carefully before you start taking this medicine because it contains important information for you. - Keep this leaflet. You may need to read it again. - If you have any further questions, ask your doctor or pharmacist. - This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. - If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4. What is in this leaflet 1. What Dostinex is and what it is used for 2. What you need to know before you take Dostinex 3. How to take Dostinex 4. Possible side effects 5 How to store Dostinex 6. Contents of the pack and other information 1. What Dostinex is and what it is used for - Dostinex contains the active ingredient cabergoline. This medicine belongs to a class of medicines called ‘dopamine agonists’. Dopamine is produced naturally in the body and helps to transmit messages to the brain. - Dostinex is used to stop breast milk production (lactation) soon after childbirth, stillbirth, abortion or miscarriage. It can also be used if you do not want to continue to breast-feed your baby once you have started. - Dostinex can also be used to treat other conditions caused by hormonal disturbance which can result in high levels of prolactin being produced. This includes lack of periods, infrequent and very light menstruation, periods in which ovulation does not occur and secretion of milk from your breast without breast-feeding. -
Anesthetics; Drugs of Abuse & Withdrawal
Anesthetics; Drugs of Abuse & Withdrawal Kurt Kleinschmidt, MD, FACEP, FACMT Professor of Emergency Medicine Section Chief and Program Director Medical Toxicology UT Southwestern Medical Center Much Thanks To… Sean M. Bryant, MD Associate Professor Cook County Hospital (Stroger) Department of Emergency Medicine Assistant Fellowship Director: Toxikon Consortium Associate Medical Director Illinois Poison Center Overview Anesthetics – Local – Inhalational – NM Blockers & Malignant Hyperthermia Drugs of Abuse (Pearls) Withdrawal History 1904-Procaine (short Duration of Action) 1925 (dibucaine) & 1928 (tetracaine) → potent, long acting 1943-lidocaine 1956-mepivacaine, 1959-prilocaine 1963-bupivacaine, 1971-etidocaine, 1996-ropivacaine Lipophili Intermediate Amine Substituents c Group Esters Structure 2 Distinct Groups 1) Amino Esters Amides 2) Amino Amides Local Anesthetics Toxic Reactions • Few & iatrogenic • Blood vessel administration or toxic dose AMIDES have largely replaced ESTERS • Increased stability • Relative absence of hypersensitivity reactions – ESTER hydrolysis = PABA (cross sensitivity) – AMIDES = Multidose preps → methylparabens • Chemically related to PABA with rare allergic reactions Local Anesthetics Mode of Action • Reversible & Predictable Binding • Within membrane-bound sodium channels of conducting tissue (cytoplasmic side of membrane) → Failure to form/propagate action potentials (Small-diam. fibersBLOCKADE carrying pain/temp sensation) Pain fibers - higher firing rate & longer AP → • ↑Sodium susceptible Channelto local -
Phoretic Analysis of Ergot Alkaloids. Relations Mobility in the Cle Vine
Acta Pharm, Suecica 2, 357 (1965) Thin-layer chromatographic and thin-layer electro- phoretic analysis of ergot alkaloids.Relations between structure, RM value and electrophoretic mobility in the cle vine series STIG AGUREll DepartMent of PharmacOgnosy, Kunql, Farmaceuliska Insiitutei, StockhOLM, Sweden SUMMARY A thin-layer chromatographic and electrophoretic study of the ergot alkaloids has been made, to find rapid methods for the separation and identification of the known ergot alkaloids. The mobilities of ergot alkaloids in several useful chromatographic and electrophore- tic systems are recorded. Relations have been observed between structure and R" value in methanol-chloroform on Silica Gel G. A simple, rapid thin-layer electrophoretic technique has been de- vised for separation of ergot alkaloids, and a relation between structure and electrophoretic mobility is evident. Two-dimensional combinations of thin-layer chromatography and thin-layer electro- phoresis and chromatography are described. Numerous paper chromatographic procedures have been published for separation of the ergot alkaloids and their derivatives. Hofmann (1) and Genest & Farmilio (2) have recently listed these systems. The general advantages of thin-layer chromatography (TLC) over paper partition chromatography are well known: shorter time of equilibration and devel- opment, generally better resolution, smaller amounts of substance rc- quired, and wider choice of reagents. Several reports of TLC of ergot alkaloids have been published. In gene- ral, these investigations (2-6 and others) have dealt 'with limited groups of alkaloids, or with a specific problem involving at most a dozen of the 40 now known naturally occurring ergot alkaloids. Some paper chromate- .357 graphic systems using Iorrnamide-treated papers have also been adopted for thin-layer chromatographic use (7, 8). -
Electronic Supplementary Material (ESI) for RSC Advances. This Journal Is © the Royal Society of Chemistry 2017
Electronic Supplementary Material (ESI) for RSC Advances. This journal is © The Royal Society of Chemistry 2017 The physicochemical properties and NMR spectra of some ergot alkaloids are summarized as following. Especially, under the influence of acids, alkaloids or light, the carbo at the position 8 of D-lysergic acid derivatives can occur isomerization which 8R is changed into 8S to form the responding isomers, lead to the formation of α-ergotaminine, ergocryptinine, ergocorninine and ergocristinine which the NMR data are shown in Table S1, S2 and S3. Clavine Agroclavine: crystal (acetone), mp 198~203℃, soluble in benzene, ethanol, slightly soluble 1 in water. Molecular formula: C16H18N2, MW m/z: 238. The data of H-NMR (Pyridine-d5,220 13 MHz) and C-NMR (Pyridine-d5,15.08 MHz) {Bach, 1974 #48}are shown in Table S1 and S2. Elymoclavine: mp 250~252℃, Molecular formula: C16H18N2O, MW m/z: 254. The data of 1 13 H-NMR (CDCl3, 220 MHz) and C-NMR (CDCl3, 15.08 MHz){Bach, 1974 #48} of its acetate derivatives are shown in Table S1 and S2. 1 Festuclavine: mp 241℃, Molecular formula: C16H18N2, MW m/z: 238. The data of H-NMR 13 (CDCl3, 220 MHz) and C-NMR (CDCl3, 15.08 MHz) {Bach, 1974 #48}are shown in Table S1 and S2. Fumigaclavine B: mp 265~267℃, Molecular formula: C16H20N2O, MW m/z: 256. The data of 1 13 H-NMR (pyridine-d5,220 MHz) and C-NMR (pyridine-d5,15.08 MHz) {Bach, 1974 #48}are shown in Table S1 and S2. Ergoamides Ergometrine: white crystal (acetone), mp 162℃. -
Ergometrine Maleate
The European Agency for the Evaluation of Medicinal Products Veterinary Medicines Evaluation Unit EMEA/MRL/237/97-FINAL June 1999 COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS ERGOMETRINE MALEATE SUMMARY REPORT 1. Ergometrine is a naturally occurring alkaloid found in ergot (Claviceps purpurea). It is classified as a water-soluble lysergic acid derivative, and is an orally-active stimulant of uterine contractions. The maleate salt (ergometrine maleate) exhibits greater stability than the free base and is the usual form in which the alkaloid is used in medicinal products. It is used in veterinary medicine in the control of postpartum uterine haemorrhage, removal of fluid from atonic uteri, to prevent pro-lapsed uteri, and judiciously in terms of timing to aid in suturing the uterus after caesarean section or in replacing an everted uterus. Dose regimens are: cows and mares: 2 to 5 mg/animal (intravenously or intramuscularly); ewes, goats and sows: 0.5 to 1 mg/animal (intramuscularly). In human medicine, it is used orally and parenterally in the prevention and treatment of postpartum haemorrhage caused by uterine atony and for the stimulation of uterine involution. Usual oral doses are 500 µg 3 times daily up to 1.8 mg daily (approximately 0.03 mg/kg bw). Ergot alkaloids have been reported to be present in flour from rye, wheat and barley in amounts ranging from 0.01 to 2.36 mg/kg flour. EU legislation restricts the maximum percentage of ergot tolerated in flour to 0.1%. Total daily human intake of ergot alkaloids from contaminated foodstuffs of plant origin has been estimated as up to 7.8 µg/person.