Recent Progress in Ergot Alkaloid Research†
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Pericardial, Retroperitoneal, and Pleural Fibrosis Induced by Pergolide
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.66.1.79 on 1 January 1999. Downloaded from J Neurol Neurosurg Psychiatry 1999;66:79–81 79 SHORT REPORT Pericardial, retroperitoneal, and pleural fibrosis induced by pergolide S Shaunak, A Wilkins, J B Pilling, D J Dick Abstract 1992, the emergence of motor fluctuations led Three patients with Parkinson’s disease to the introduction of pergolide, and the dose are described who developed pericardial, of this was gradually increased to a maximum retroperitoneal, and pleural fibrosis asso- of 1mg/day. 1n 1994, 2 years after the ciated with pergolide treatment. Surgical introduction of pergolide, the patient devel- intervention was required in all three oped left flank pain with weight loss, and was cases, either to reach a tissue diagnosis or found to have a mild anaemia (haemoglobin for potentially life threatening complica- 10.4 g/dl), with indices suggesting iron defi- tions. Symptoms emerged on average 2 ciency, and an ESR of 40 mm/h. Upper gastro- years after the institution of treatment, intestinal endoscopy and barium enema gave and were suYciently non-specific to cause negative results. Seven months later right sided significant delays in diagnosis in all cases. chest pain and a non-productive cough devel- The erythrocyte sedimentation rate (ESR) oped; investigations confirmed persistent anae- was raised in the two patients in whom it mia, an ESR of 55 mm/h, and bilateral pleural was measured. Serosal fibrosis is a rarely thickening on chest radiography and CT. Lung reported adverse eVect of pergolide treat- function tests showed a reduction in total lung ment, although it is well described with capacity of 36% with no fall in transfer factor, other dopamine agonists. -
Evidence from Horses with Pituitary Pars Intermedia Dysfunction Jessica S
Fortin et al. BMC Veterinary Research (2020) 16:356 https://doi.org/10.1186/s12917-020-02565-3 RESEARCH ARTICLE Open Access Restoring pars intermedia dopamine concentrations and tyrosine hydroxylase expression levels with pergolide: evidence from horses with pituitary pars intermedia dysfunction Jessica S. Fortin1*, Matthew J. Benskey2, Keith J. Lookingland2, Jon S. Patterson1, Erin B. Howey1, John L. Goudreau2,3 and Harold C. Schott II4* Abstract Background: Pituitary pars intermedia dysfunction (PPID) develops slowly in aged horses as degeneration of hypothalamic dopaminergic neurons leads to proliferation of pars intermedia (PI) melanotropes through hyperplasia and adenoma formation. Dopamine (DA) concentrations and tyrosine hydroxylase (TH) immunoreactivity are markedly reduced in PI tissue of PPID-affected equids and treatment with the DA receptor agonist pergolide results in notable clinical improvement. Thus, we hypothesized that pergolide treatment of PPID-affected horses would result in greater DA and TH levels in PI tissue collected from PPID-affected horses versus untreated PPID-affected horses. To test this hypothesis, pituitary glands were removed from 18 horses: four untreated PPID-affected horses, four aged and four young horses without signs of PPID, and six PPID-affected horses that had been treated with pergolide at 2 µg/kg orally once daily for 6 months. DA concentrations and TH expression levels in PI tissues were determined by high performance liquid chromatography with electrochemical detection and Western blot analyses, respectively. Results: DA and TH levels were lowest in PI collected from untreated PPID-affected horses while levels in the pergolide treated horses were similar to those of aged horses without signs of PPID. -
WO 2014/106238 Al 3 July 2014 (03.07.2014) P O P C T
(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 WO 2014/106238 Al 3 July 2014 (03.07.2014) P O P C T (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 31/404 (2006.01) C07D 209/04 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, A61P 25/18 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (21) International Application Number: KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, PCT/US2013/078453 MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (22) International Filing Date: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 3 1 December 2013 (3 1.12.2013) SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (25) Filing Language: English ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 61/747,499 31 December 2012 (3 1. 12.2012) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (71) Applicant: FANG, Qun, Kevin [US/US]; 34 Atwood TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, Street, Westfield, MA 02482 (US). -
Progress and Prospects of Ergot Alkaloid Research
Progress and Prospects of Ergot Alkaloid Research Joydeep Mukherjee, Miriam Menge Institut für Technische Chemie, Universität Hannover, Callinstr. 3, D-30167 Hannover, Germany E-mail: [email protected] Ergot alkaloids, produced by the plant parasitic fungi Claviceps purpurea are important pharmaceuticals. The chemistry, biosynthesis, bioconversions, physiological controls, and biochemistry have been extensively reviewed by earlier authors.We present here the research done on the organic synthesis of the ergot alkaloids during the past two decades. Our aim is to apply this knowledge to the synthesis of novel synthons and thus obtain new molecules by directed biosynthesis. The synthesis of clavine alkaloids, lysergic acid derivatives, the use of tryptophan as the starting material, the chemistry of 1,3,4,5-tetrahydrobenzo[cd]indoles, and the structure activity relationships for ergot alkaloids have been discussed. Recent advances in the molecular biology and enzymology of the fungus are also mentioned. Application of oxygen vectors and mathematical modeling in the large scale production of the alkaloids are also discussed. Finally, the review gives an overview of the use of modern analytical methods such as capillary electrophoresis and two-dimensional fluorescence spectroscopy. Keywords. Ergot, Alkaloid synthesis, Claviceps, Directed biosynthesis, Bioreactors 1Introduction . 2 2 Chemistry, Bioconversions, and Directed Biosynthesis . 2 2.1 Chemical Synthesis . 3 2.1.1 Chemical Structures . 3 2.1.1.1 Clavine Alkaloids . 3 2.1.1.2 Simple Lysergic Acid Derivatives . 4 2.1.1.3 Ergopeptines . 4 2.1.1.4 Ergopeptams . 5 2.1.2 Synthesis of Clavine Alkaloids and Lysergic Acid Derivatives . 5 2.1.3 Use of Tryptophan as the Starting Material . -
Near the Himalayas, from Kashmir to Sikkim, at Altitudes the Catholic Inquisition, and the Traditional Use of These of up to 2700 Meters
Year of edition: 2018 Authors of the text: Marc Aixalà & José Carlos Bouso Edition: Alex Verdaguer | Genís Oña | Kiko Castellanos Illustrations: Alba Teixidor EU Project: New Approaches in Harm Reduction Policies and Practices (NAHRPP) Special thanks to collaborators Alejandro Ponce (in Peyote report) and Eduardo Carchedi (in Kambó report). TECHNICAL REPORT ON PSYCHOACTIVE ETHNOBOTANICALS Volumes I - II - III ICEERS International Center for Ethnobotanical Education Research and Service INDEX SALVIA DIVINORUM 7 AMANITA MUSCARIA 13 DATURA STRAMONIUM 19 KRATOM 23 PEYOTE 29 BUFO ALVARIUS 37 PSILOCYBIN MUSHROOMS 43 IPOMOEA VIOLACEA 51 AYAHUASCA 57 IBOGA 67 KAMBÓ 73 SAN PEDRO 79 6 SALVIA DIVINORUM SALVIA DIVINORUM The effects of the Hierba Pastora have been used by Mazatec Indians since ancient times to treat diseases and for divinatory purposes. The psychoactive compound Salvia divinorum contains, Salvinorin A, is the most potent naturally occurring psychoactive substance known. BASIC INFO Ska Pastora has been used in divination and healing Salvia divinorum is a perennial plant native to the Maza- rituals, similar to psilocybin mushrooms. Maria Sabina tec areas of the Sierra Madre Oriental Mountains of Mexi- told Wasson and Hofmann (the discoverers of its Mazatec co. Its habitat is tropical forests, where it grows between usage) that Salvia divinorum was used in times when the- 300 and 800 meters above sea level. It belongs to the re was a shortage of mushrooms. Some sources that have Lamiaceae family, and is mainly reproduced by cuttings done later feldwork point out that the use of S. divinorum since it rarely produces seeds. may be more widespread than originally believed, even in times when mushrooms were abundant. -
Biased Ligands Differentially Shape the Conformation of The
International Journal of Molecular Sciences Article Biased Ligands Differentially Shape the Conformation of the Extracellular Loop Region in 5-HT2B Receptors Katrin Denzinger, Trung Ngoc Nguyen, Theresa Noonan, Gerhard Wolber and Marcel Bermudez * Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Strasse 2-4, 14195 Berlin, Germany; [email protected] (K.D.); [email protected] (T.N.N.); [email protected] (T.N.); [email protected] (G.W.) * Correspondence: [email protected] Received: 22 November 2020; Accepted: 18 December 2020; Published: 20 December 2020 Abstract: G protein-coupled receptors are linked to various intracellular transducers, each pathway associated with different physiological effects. Biased ligands, capable of activating one pathway over another, are gaining attention for their therapeutic potential, as they could selectively activate beneficial pathways whilst avoiding those responsible for adverse effects. We performed molecular dynamics simulations with known β-arrestin-biased ligands like lysergic acid diethylamide and ergotamine in complex with the 5-HT2B receptor and discovered that the extent of ligand bias is directly connected with the degree of closure of the extracellular loop region. Given a loose allosteric coupling of extracellular and intracellular receptor regions, we delineate a concept for biased signaling at serotonin receptors, by which conformational interference with binding pocket closure restricts the signaling repertoire of the receptor. Molecular docking studies of biased ligands gathered from the BiasDB demonstrate that larger ligands only show plausible docking poses in the ergotamine-bound structure, highlighting the conformational constraints associated with bias. This emphasizes the importance of selecting the appropriate receptor conformation on which to base virtual screening workflows in structure-based drug design of biased ligands. -
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). -
Ergot Alkaloid Biosynthesis in Aspergillus Fumigatus : Association with Sporulation and Clustered Genes Common Among Ergot Fungi
Graduate Theses, Dissertations, and Problem Reports 2009 Ergot alkaloid biosynthesis in Aspergillus fumigatus : Association with sporulation and clustered genes common among ergot fungi Christine M. Coyle West Virginia University Follow this and additional works at: https://researchrepository.wvu.edu/etd Recommended Citation Coyle, Christine M., "Ergot alkaloid biosynthesis in Aspergillus fumigatus : Association with sporulation and clustered genes common among ergot fungi" (2009). Graduate Theses, Dissertations, and Problem Reports. 4453. https://researchrepository.wvu.edu/etd/4453 This Dissertation is protected by copyright and/or related rights. It has been brought to you by the The Research Repository @ WVU with permission from the rights-holder(s). You are free to use this Dissertation in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you must obtain permission from the rights-holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/ or on the work itself. This Dissertation has been accepted for inclusion in WVU Graduate Theses, Dissertations, and Problem Reports collection by an authorized administrator of The Research Repository @ WVU. For more information, please contact [email protected]. Ergot alkaloid biosynthesis in Aspergillus fumigatus: Association with sporulation and clustered genes common among ergot fungi Christine M. Coyle Dissertation submitted to the Davis College of Agriculture, Forestry, and Consumer Sciences at West Virginia University in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Genetics and Developmental Biology Daniel G. Panaccione, Ph.D., Chair Kenneth P. Blemings, Ph.D. Joseph B. -
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). -
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. -
Diversification of Ergot Alkaloids in Natural and Modified Fungi
Toxins 2015, 7, 201-218; doi:10.3390/toxins7010201 OPEN ACCESS toxins ISSN 2072-6651 www.mdpi.com/journal/toxins Review Diversification of Ergot Alkaloids in Natural and Modified Fungi Sarah L. Robinson and Daniel G. Panaccione * Division of Plant and Soil Sciences, West Virginia University, Morgantown, WV 26506, USA; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +1-304-293-8819; Fax: +1-304-293-2960. Academic Editor: Christopher L. Schardl Received: 21 November 2014 / Accepted: 14 January 2015 / Published: 20 January 2015 Abstract: Several fungi in two different families––the Clavicipitaceae and the Trichocomaceae––produce different profiles of ergot alkaloids, many of which are important in agriculture and medicine. All ergot alkaloid producers share early steps before their pathways diverge to produce different end products. EasA, an oxidoreductase of the old yellow enzyme class, has alternate activities in different fungi resulting in branching of the pathway. Enzymes beyond the branch point differ among lineages. In the Clavicipitaceae, diversity is generated by the presence or absence and activities of lysergyl peptide synthetases, which interact to make lysergic acid amides and ergopeptines. The range of ergopeptines in a fungus may be controlled by the presence of multiple peptide synthetases as well as by the specificity of individual peptide synthetase domains. In the Trichocomaceae, diversity is generated by the presence or absence of the prenyl transferase encoded by easL (also called fgaPT1). Moreover, relaxed specificity of EasL appears to contribute to ergot alkaloid diversification. The profile of ergot alkaloids observed within a fungus also is affected by a delayed flux of intermediates through the pathway, which results in an accumulation of intermediates or early pathway byproducts to concentrations comparable to that of the pathway end product. -
Impact of Ergot Alkaloid and Estradiol 17B on Whole-Body Protein Turnover and Expression of Mtor Pathway Proteins in Muscle of Cattle
University of Kentucky UKnowledge Theses and Dissertations--Animal and Food Sciences Animal and Food Sciences 2020 Impact of Ergot Alkaloid and Estradiol 17B on Whole-Body Protein Turnover and Expression of mTOR Pathway Proteins in Muscle of Cattle Taylor Dawn Ferguson University of Kentucky, [email protected] Author ORCID Identifier: https://orcid.org/0000-0001-6598-4133 Digital Object Identifier: https://doi.org/10.13023/etd.2020.459 Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Ferguson, Taylor Dawn, "Impact of Ergot Alkaloid and Estradiol 17B on Whole-Body Protein Turnover and Expression of mTOR Pathway Proteins in Muscle of Cattle" (2020). Theses and Dissertations--Animal and Food Sciences. 122. https://uknowledge.uky.edu/animalsci_etds/122 This Master's Thesis is brought to you for free and open access by the Animal and Food Sciences at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Animal and Food Sciences by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained needed written permission statement(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine) which will be submitted to UKnowledge as Additional File.