Analysis of L-Dopa Induced Dyskinesias in 51 Patients with Parkinsonism

Total Page:16

File Type:pdf, Size:1020Kb

Analysis of L-Dopa Induced Dyskinesias in 51 Patients with Parkinsonism J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.34.6.668 on 1 December 1971. Downloaded from J. Neurol. Neurosurg. Psychiat., 1971, 34, 668-673 Analysis of L-dopa induced dyskinesias in 51 patients with Parkinsonism R. J. MONES, T. S. ELIZAN, AND G. J. SIEGEL From the Department of Neurology, Mount Sinai Medical School, New York, New York, U.S.A. SUMMARY An analysis of 51 patients with Parkinsonism who have developed L-dopa induced dyskinesias is presented. The cause has not been proven, although various hypotheses are discussed. One third of the total number of patients treated developed dyskinesia. These patients tend to re- spond better to L-dopa than the other group. There is a tendency for the older patient or the patient with long-standing disease to develop dyskinesias. There appears to be no way of predicting which patients will develop dyskinesia by analysis of the symptoms or the aetiology of the Parkinsonism syndrome. The unilateral characteristic of the dyskinesia in patients with hemi-Parkinsonism and patients with unilateral thalamotomies suggests that structural abnormalities are critical in deter-guest. Protected by copyright. mining the presence and localization of dyskinesias. This is supported by non-occurrence of similarly treated patients without Parkinsonism. L-dopa is now established as the treatment of choice and 45 started in the hospital. The protocol for the medical for Parkinsonism. Many articles have appeared in and neurological evaluation of these patients, the follow- the literature since the initial work of Cotzias, up care, and the laboratory data are included in a pre- Van vious paper (Mones, 1969). The dyskinesias were evaluated Woert, and Schiffer (1967), Cotzias, Papava- by clinical history, neurological examination and by siliou, and Gellene (1969) concerning the use of cin6 films of selected patients. The dosage of L-dopa chronic high dose oral treatment with L-dopa. was between 3 and 6 g per day and the longest treatment Most authors have found the drug of great help period in this series is 12 months. in approximately 50% of patients (Duvoisin, Barrett, Schear, Hoehn, and Yahr, 1969; Yahr, Duvoisin, RESULTS Schear, Barrett, and Hoehn, 1969; Mones and Elizan, 1969; Elizan and Siegel, 1970). These Involuntary irregular movements have been observed patients have a change in their life style and a during L-dopa therapy in 51 patients. These are definite improvement in their symptoms in the most commonly seen in the facial muscles, jaw, periods of at least one to three years of observation. tongue, and neck, and consist of irregular fast and It has not yet been established if the drug stops the slow movements which can be categorized as ahttp://jnnp.bmj.com/ progression of the disease on a long-term basis. combination of choreiform movements, athetosis, One of the most important and fascinating compli- and dystonia. These dyskinesias are irregular, occur cations of the drug is the induction of dyskinesias. at different times of the day, but most commonly This paper is an analysis of L-dopa induced dyskine- are decreased or absent in the morning hours. sias seen in 51 patients with Parkinsonism treated Other abnormalities have been noted, including at the Mount Sinai Medical Center. dystonic movements of the limbs and involuntary flexion of the toes. Other more bizarre movements METHODS of the trunk, with irregular hip or shoulder move- on October 2, 2021 by ments, have been seen. Less common are abnormal The patients in this series of 152 were treated at the Mount Sinai Medical Center, from 1 November 1968 respirations such as panting or sighing respiration to 31 October 1969. The initial 60 patients were all and forced inspiratory spasms and dyspnoea. first treated in the hospital and then followed as out- Involuntary eye movements have not been seen. patients on a monthly basis. Of the next 90 patients, 45 These patients are frequently not aware of early have had treatment started in the outpatient department minor facial dyskinesias, but later these movements 668 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.34.6.668 on 1 December 1971. Downloaded from Analysis Of L-dopa induced dyskinesia in 51 patients with Parkinsonism 669 may become embarrassing and a severe disability. is also indicated. The majority of patients developed In 25 of the 51 cases, the dyskinesias limited the their dyskinesias while on a dosage of 3 to 6 g amount of L-dopa that could be given and decreased daily. Most ofthe patients developedtheir dyskinesias the efficacy of the drug. by the fifth month of therapy. A total of 152 patients were started on L-dopa Table 1 lists the relationship of the induction of at the Mount Sinai Medical Center up to 31 July dyskinesias to the improvement of the patient on 1969 (Table 1). These cases of Parkinson's disease L-dopa therapy. The criteria for improvement have have been evaluated for this study, as they had been relatively simple. Patients are considered to have been on the drug for at least three months. By (1) no improvement, (2) mild improvement, (3) good 31 October 1969, 51 cases had developed dyskinesias improvement, implying a change in life style so that at some time during their L-dopa therapy. None if the patient was unable to work he is now working, of 12 patients with various diseases of the nervous or if the patient was unable to care for himself, he is system other than Parkinsonism who have been now able to care for himself, or (4) dramatic im- started on L-dopa developed induced dyskinesias. provement. Of 152 cases, 13 patients had a dra- The dosage of the drug at the time of the onset matic improvement on the drug, and of these 13, 11 of dyskinesias is shown in Table 2. The month of had some type of dyskinesia (Table 1). Sixty-three L-dopa therapy in which the dyskinesias occurred cases had a good result with L-dopa therapy, and 28 of these had induced dyskinesias. Of 37 patients who had mild improvement on the drug, only 11 TABLE 1 had induced dyskinesias. Of 22 patients who had no help from L-dopa, only one patient developed PATIENTS WITH PARKINSONISM EVALUATED (152) dyskinesias. It appears that patients who do well guest. Protected by copyright. A. Improved with L-dopa Induced dvskinesias with L-dopa have a high percentage of induced dyskinesias. This may imply that the improvement Dramatic 13 11 of a patient on L-dopa therapy is related in some way Good 63 28 Mild 37 11 to the induction of dyskinesias. It must be noted, however, that many patients with dramatic improve- B. No help 22 1 ment or good improvement in their Parkinson's C. Stopped L-dopa 17 0 disease did not develop dyskinesias. Died 6 The cause of Parkinsonism was analysed in this Cardiac problems 2 Psychiatric problems 3 series. Seven patients had post-encephalitic Parkin- Rash I sonism and of these, five showed significant clinical Fever 1 Other causes 4 improvement and two developed dyskinesias. Of the idiopathic type represented by 145 cases, 71 152 51 improved significantly and 49 developed dyskinesias. No conclusion can be drawn relating type of Parkinsonism to induction of dyskinesias. Nine patients in this series had bilateral thala- TABLE 2 motomies and only one patient developed dyskine- DEVELOPMENT OF L-DOPA INDUCED DYSKINESIA RELATED sias, which is a figure much lower than the general TO MONTH AND DRUG AND DOSAGE LEVEL AT TIME OF ON- overall percentage (Table 3). This patient developed SET OF DYSKINESIAS bilateral facial grimacing and respiratory abnormali- http://jnnp.bmj.com/ Months on L-dopa L-dopa dose (glday) at onset of dyskinesias ties. Thirteen patients had previous unilateral thala- motomies, and of these seven developed dyskinesias. 1-2 2-3 3-4 4-5 5-6 6-7 Totals 1 2 1 7 1 2 11 TABLE 3 3 1 7 1 3 12 4 1 4 4 4 13 EFFECT OF PREVIOUS THALAMOTOMY FOR PARKINSONISM 5 2 1 3 1 7 6 1 2 3 Patients Significant L-dopa 7 3 1 4 (no.) clinical induced on October 2, 2021 by 8 1 1 improvement dyskinesia 9 (L-dopa) 10 11 Bilateral operation 9 6 l 12 Unilateral operation 13 5 7 Non-operated Totals 3 25 8 14 1 patients 130 65 43 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.34.6.668 on 1 December 1971. Downloaded from 670 R. J. Mones, T. S. Elizan, and G. J. Siegel There were no unilateral limb dyskinesias seen TABLE 6 contralateral to the thalamotomy. Five patients who did PREDOMINANT ABNORMALITIES IN THE PATIENTS WITH have unilateral limb dyskinesias all had PARKINSONISM WHO DEVELOPED L-DOPA INDUCED DYSKIN- their movements ipsilateral to -the thalamotomy. ESIAS Table 4-shows that there-is-no definite statistical correlation between dyskinesia and duration of Tremor 13 Akinesia 10 Parkinson's disease before L-dopa. However, it Gait 17 appears that the longer the disease has been present, Face and speech 2 Rigidity 4 the greater the incidence of L-dopa induced dys- Fine movements 4 kinesias. Posture 1 The relationship of dyskinesias to severity of the Total 51 Parkinson's disease was analysed (Table 5). Patients graded as having a mild disease have evidence of extrapyramidal syndrome but are not disabled and can do their normal work or housework; moderate Table 7 analyses the relationship with age on Parkinsonisni implies difficulty in working, but starting L-dopa therapy. No conclusion is possible, some ability to care for themselves in their every- although it is noted that the percentage of dyskinesias day living activities; severe Parkinsonism implies in the oldest age group is low.
Recommended publications
  • Anti-Cholinergic Alkaloids As Potential Therapeutic Agents for Alzheimer's Disease
    Indian Journal of Biochemistry & Biophysics Vol. 50, April 2013, pp. 120-125 Anti-cholinergic alkaloids as potential therapeutic agents for Alzheimer’s disease: An in silico approach Huma Naaz, Swati Singh, Veda P Pandey, Priyanka Singh and Upendra N Dwivedi* Bioinformatics Infrastructure Facility, Center of Excellence in Bioinformatics, Department of Biochemistry, University of Lucknow, Lucknow 226 007, India Received 10 September 2012; revised 25 January 2013 Alzheimer’s disease (AD), a progressive neurodegenerative disorder with many cognitive and neuropsychiatric symptoms is biochemically characterized by a significant decrease in the brain neurotransmitter acetylcholine (ACh). Plant-derived metabolites, including alkaloids have been reported to possess neuroprotective properties and are considered to be safe, thus have potential for developing effective therapeutic molecules for neurological disorders, such as AD. Therefore, in the present study, thirteen plant-derived alkaloids, namely pleiocarpine, kopsinine, pleiocarpamine (from Pleiocarpa mutica, family: Annonaceae), oliveroline, noroliveroline, liridonine, isooncodine, polyfothine, darienine (from Polyalthia longifolia, family: Apocynaceae) and eburnamine, eburnamonine, eburnamenine and geissoschizol (from Hunteria zeylanica, family: Apocynaceae) were analyzed for their anti-cholinergic action through docking with acetylcholinesterase (AChE) as target. Among the alkaloids, pleiocarpine showed promising anti-cholinergic potential, while its amino derivative showed about six-fold
    [Show full text]
  • 5994392 Tion of Application No. 67375.734 Eb3-1685, PEN. T
    USOO5994392A United States Patent (19) 11 Patent Number: 5,994,392 Shashoua (45) Date of Patent: Nov.30, 1999 54 ANTIPSYCHOTIC PRODRUGS COMPRISING 5,120,760 6/1992 Horrobin ................................. 514/458 AN ANTIPSYCHOTICAGENT COUPLED TO 5,141,958 8/1992 Crozier-Willi et al. ................ 514/558 AN UNSATURATED FATTY ACID 5,216,023 6/1993 Literati et al. .......................... 514/538 5,246,726 9/1993 Horrobin et al. ....................... 424/646 5,516,800 5/1996 Horrobin et al. ....................... 514/560 75 Inventor: Victor E. Shashoua, Brookline, Mass. 5,580,556 12/1996 Horrobin ................................ 424/85.4 73 Assignee: Neuromedica, Inc., Conshohocken, Pa. FOREIGN PATENT DOCUMENTS 30009 6/1981 European Pat. Off.. 21 Appl. No.: 08/462,820 009 1694 10/1983 European Pat. Off.. 22 Filed: Jun. 5, 1995 09 1694 10/1983 European Pat. Off.. 91694 10/1983 European Pat. Off.. Related U.S. Application Data 59-025327 2/1984 Japan. 1153629 6/1989 Japan. 63 Continuation of application No. 08/080,675, Jun. 21, 1993, 1203331 8/1989 Japan. abandoned, which is a continuation of application No. 07/952,191, Sep. 28, 1992, abandoned, which is a continu- (List continued on next page.) ation of application No. 07/577,329, Sep. 4, 1990, aban doned, which is a continuation-in-part of application No. OTHER PUBLICATIONS 07/535,812,tion of application Jun. 11, No. 1990, 67,375.734 abandoned, Eb3-1685, which is a continu-PEN. T. Higuchi et al. 66 Prodrugs as Noye Drug Delivery Sys 4,933,324, which is a continuation-in-part of application No.
    [Show full text]
  • Charles University in Prague, Faculty of Pharmacy in Hradec Kralove Department of Pharmaceutical Botany and Ecology DIPLOMA TH
    Charles University in Prague, Faculty of Pharmacy In Hradec Kralove Department of Pharmaceutical Botany and Ecology ______________________________________________________________________ DIPLOMA THESIS Biological Activity of Plant Metabolites XVII. Alkaloids of Corydalis yanhusuo W.T. Wang Supervisor of Diploma Work: Assoc. Prof. RNDr. Lubomir Opletal, CSc. Head of Department: Prof. RNDr. Luděk Jahodář, CSc. Hradec Králové April, 2011 Gabriella Cipra Declaration I declare that this thesis is my original copyrighted work. All literature and other sources from which I extracted my research in the process are listed in the bibliography and all work is properly cited. This work has not been used to gain another or same title. Acknowledgements I wish to express my deepest gratitude, first and foremost to Assoc. Prof. RNDr. Lubomír Opletal, CSc. for all his guidance, support and enthusiasm with the preparation of this thesis. I would also like to thank the Department of Pharmaceutical Botany and Ecology for the pleasant working environment, as well as Assoc. Prof. PharmDr. Jiří Kuneš, Ph.D. for preparation and interpretation of NMR spectra, Ing. Kateřina Macáková for biological activity measurements, and Ing. Lucie Cahlíková, Ph.D. for MS spectra measurements and interpretations. This work was financially supported by Specific University Research Foundation No SVV-2011-263002 (Study of biologically active compounds in prespective of their prevention and treatment in civil diseases) Table of Contents 1 INTRODUCTION 7 2 AIM OF WORK 10 3 THEORETICAL
    [Show full text]
  • Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Sedative
    Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Sedative Chemical Dosage (+)-BORNYL-ISOVALERATE -- (-)-DICENTRINE LD50=187 1,8-CINEOLE -- 2-METHYLBUT-3-ENE-2-OL -- 6-GINGEROL -- 6-SHOGAOL -- ACYLSPINOSIN -- ADENOSINE -- AKUAMMIDINE -- ALPHA-PINENE -- ALPHA-TERPINEOL -- AMYL-BUTYRATE -- AMYLASE -- ANEMONIN -- ANGELIC-ACID -- ANGELICIN ED=20-80 ANISATIN 0.03 mg/kg ANNOMONTINE -- APIGENIN 30-100 mg/kg ARECOLINE 1 mg/kg ASARONE -- ASCARIDOLE -- ATHEROSPERMINE -- BAICALIN -- BALDRINAL -- BENZALDEHYDE -- BENZYL-ALCOHOL -- Chemical Dosage BERBERASTINE -- BERBERINE -- BERGENIN -- BETA-AMYRIN-PALMITATE -- BETA-EUDESMOL -- BETA-PHENYLETHANOL -- BETA-RESERCYCLIC-ACID -- BORNEOL -- BORNYL-ACETATE -- BOSWELLIC-ACID 20-55 mg/kg ipr rat BRAHMINOSIDE -- BRAHMOSIDE -- BULBOCAPNINE -- BUTYL-PHTHALIDE -- CAFFEIC-ACID 500 mg CANNABIDIOLIC-ACID -- CANNABINOL ED=200 CARPACIN -- CARVONE -- CARYOPHYLLENE -- CHELIDONINE -- CHIKUSETSUSAPONIN -- CINNAMALDEHYDE -- CITRAL ED 1-32 mg/kg CITRAL 1 mg/kg CITRONELLAL ED=1 mg/kg CITRONELLOL -- 2 Chemical Dosage CODEINE -- COLUBRIN -- COLUBRINOSIDE -- CORYDINE -- CORYNANTHEINE -- COUMARIN -- CRYOGENINE -- CRYPTOCARYALACTONE 250 mg/kg CUMINALDEHYDE -- CUSSONOSIDE-A -- CYCLOSTACHINE-A -- DAIGREMONTIANIN -- DELTA-9-THC 10 mg/orl/man/day DESERPIDINE -- DESMETHOXYANGONIN 200 mg/kg ipr DIAZEPAM 40-200 ug/lg/3-4x/day DICENTRINE LD50=187 DIDROVALTRATUM -- DIHYDROKAWAIN -- DIHYDROMETHYSTICIN 60 mg/kg ipr DIHYDROVALTRATE -- DILLAPIOL ED50=1.57 DIMETHOXYALLYLBENZENE -- DIMETHYLVINYLCARBINOL -- DIPENTENE
    [Show full text]
  • Diversity of the Mountain Flora of Central Asia with Emphasis on Alkaloid-Producing Plants
    diversity Review Diversity of the Mountain Flora of Central Asia with Emphasis on Alkaloid-Producing Plants Karimjan Tayjanov 1, Nilufar Z. Mamadalieva 1,* and Michael Wink 2 1 Institute of the Chemistry of Plant Substances, Academy of Sciences, Mirzo Ulugbek str. 77, 100170 Tashkent, Uzbekistan; [email protected] 2 Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany; [email protected] * Correspondence: [email protected]; Tel.: +9-987-126-25913 Academic Editor: Ipek Kurtboke Received: 22 November 2016; Accepted: 13 February 2017; Published: 17 February 2017 Abstract: The mountains of Central Asia with 70 large and small mountain ranges represent species-rich plant biodiversity hotspots. Major mountains include Saur, Tarbagatai, Dzungarian Alatau, Tien Shan, Pamir-Alai and Kopet Dag. Because a range of altitudinal belts exists, the region is characterized by high biological diversity at ecosystem, species and population levels. In addition, the contact between Asian and Mediterranean flora in Central Asia has created unique plant communities. More than 8100 plant species have been recorded for the territory of Central Asia; about 5000–6000 of them grow in the mountains. The aim of this review is to summarize all the available data from 1930 to date on alkaloid-containing plants of the Central Asian mountains. In Saur 301 of a total of 661 species, in Tarbagatai 487 out of 1195, in Dzungarian Alatau 699 out of 1080, in Tien Shan 1177 out of 3251, in Pamir-Alai 1165 out of 3422 and in Kopet Dag 438 out of 1942 species produce alkaloids. The review also tabulates the individual alkaloids which were detected in the plants from the Central Asian mountains.
    [Show full text]
  • Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Dry Mouth / Xerostomia
    Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Dry Mouth / Xerostomia Chemical Activity Count (+)-CATECHIN 2 (+)-EPIPINORESINOL 1 (-)-ANABASINE 1 (-)-EPICATECHIN 2 (-)-EPIGALLOCATECHIN 2 (-)-EPIGALLOCATECHIN-GALLATE 2 (Z)-1,3-BIS(4-HYDROXYPHENYL)-1,4-PENTADIENE 1 1,8-CINEOLE 2 10-METHOXYCAMPTOTHECIN 1 16-HYDROXY-4,4,10,13-TETRAMETHYL-17-(4-METHYL-PENTYL)-HEXADECAHYDRO- 1 CYCLOPENTA[A]PHENANTHREN-3-ONE 2,3-DIHYDROXYBENZOIC-ACID 1 3'-O-METHYL-CATECHIN 1 3-ACETYLACONITINE 1 3-O-METHYL-(+)-CATECHIN 1 4-O-METHYL-GLUCURONOXYLAN 1 5,7-DIHYDROXY-2-METHYLCHROMONE-8-C-BETA-GLUCOPYRANOSIDE 1 5-HYDROXYTRYPTAMINE 1 5-HYDROXYTRYPTOPHAN 1 6-METHOXY-BENZOLINONE 1 ACEMANNAN 1 ACETYL-CHOLINE 1 ACONITINE 2 ADENOSINE 2 AFFINISINE 1 AGRIMONIIN 1 ALANTOLACTONE 2 ALKANNIN 1 Chemical Activity Count ALLANTOIN 1 ALLICIN 2 ALLIIN 2 ALLOISOPTEROPODINE 1 ALLOPTEROPODINE 1 ALLOPURINOL 1 ALPHA-LINOLENIC-ACID 1 ALPHA-TERPINEOL 1 ALPHA-TOCOPHEROL 2 AMAROGENTIN 1 AMELLIN 1 ANABASINE 1 ANDROMEDOTOXIN 1 ANETHOLE 1 ANTHOCYANIDINS 1 ANTHOCYANINS 1 ANTHOCYANOSIDE 1 APIGENIN 1 APOMORPHINE 1 ARABINO-3,6-GALACTAN-PROTEIN 1 ARABINOGALACTAN 1 ARACHIDONIC-ACID 1 ARCTIGENIN 2 ARECOLINE 1 ARGLABRIN 1 ARISTOLOCHIC-ACID 1 ARISTOLOCHIC-ACID-I 1 2 Chemical Activity Count ARMILLARIEN-A 1 ARTEMISININ 1 ASCORBIC-ACID 4 ASTRAGALAN-I 1 ASTRAGALAN-II 1 ASTRAGALAN-III 1 ASTRAGALIN 1 AURICULOSIDE 1 BAICALEIN 1 BAICALIN 1 BAKUCHIOL 1 BENZALDEHYDE 1 BERBAMINE 1 BERBERASTINE 3 BERBERINE 3 BERBERINE-CHLORIDE 1 BERBERINE-IODIDE 1 BERBERINE-SULFATE 1 BETA-AMYRIN-PALMITATE
    [Show full text]
  • Comparison of Phencyclidine and Related Substances with Various Indole, Phenethylamine, and Other Psychotomimetics
    VOL ZZ, NO, i), reee 973 Comparison of Phencyclidine and chemical subtypes include PCP-like com- pounds, dioxalanes, benzomorphans, and un- Related Substances With Various bridged and bridged benz(f)isoquinolines, all Indole, Phenethylamine, and Other of which have been called "phencyclinoids" Psychotomimetics 1,2 and/or "sigma" opioids (for SKF 10,047). Substances with other heterocyclic structures also produce psychotomimetic effects in- Edward F. Domino, M.D.3 cluding 6) cannabinoids like ~9-THC, the ac- tive ingredient in marijuana, 7) ~-carbolines like harmine and harmaline, 8) some of the constituents of nutmeg including myristic in Introduction and elemicin, and 9) catatonic producing Psychotomimetics are logically classified on agents such as bulbocapnine. the basis of chemical structure. They include: l~ Indolealkyla~ines such as tryptamine, Prototypic Chemical Structures of Various dimethyltryptamine (DMT), 5-methoxydi- Substances Showing PCP-Like Activity methyl tryptamine (5-MeODMT), psilocin, etc. 2) Lysergic acid amides (also called As mentioned above, a number of chemi- lysergimides) such as lysergic acid diethyl- cals with different molecular structures have amide-25 (LSD-25) or LSD for short. LSD PCP-like effects. All of these have been test- cont~ins an indol~ structure and is frequently ed in animals. Only some of these have been classlfi,ed as an mdole hallucinogen. How- v~rified to be si!llilar in man. The compounds ever, Its more complex chemical structure WIth prototypIC structures include those warrants a separate classification. Further- shown in Figure 1. An important chemical more, it is much more difficult to synthesize pr,oblem is to establish the absolute configur- and therefore to obtain illicitly.
    [Show full text]
  • Toxins and Signalling Evelyne Benoit, Françoise Goudey-Perriere, P
    Toxins and Signalling Evelyne Benoit, Françoise Goudey-Perriere, P. Marchot, Denis Servent To cite this version: Evelyne Benoit, Françoise Goudey-Perriere, P. Marchot, Denis Servent. Toxins and Signalling. SFET Publications, Châtenay-Malabry, France, pp.204, 2009. hal-00738643 HAL Id: hal-00738643 https://hal.archives-ouvertes.fr/hal-00738643 Submitted on 21 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Collection Rencontres en Toxinologie © E. JOVER et al. TTooxxiinneess eett SSiiggnnaalliissaattiioonn -- TTooxxiinnss aanndd SSiiggnnaalllliinngg © B.J. LAVENTIE et al. Comité d’édition – Editorial committee : Evelyne BENOIT, Françoise GOUDEY-PERRIERE, Pascale MARCHOT, Denis SERVENT Société Française pour l'Etude des Toxines French Society of Toxinology Illustrations de couverture – Cover pictures : En haut – Top : Les effets intracellulaires multiples des toxines botuliques et de la toxine tétanique - The multiple intracellular effects of the BoNTs and TeNT. (Copyright Emmanuel JOVER, Fréderic DOUSSAU, Etienne LONCHAMP, Laetitia WIOLAND, Jean-Luc DUPONT, Jordi MOLGÓ, Michel POPOFF, Bernard POULAIN) En bas - Bottom : Structure tridimensionnelle de l’alpha-toxine staphylocoque - Tridimensional structure of staphylococcal alpha-toxin. (Copyright Benoit-Joseph LAVENTIE, Daniel KELLER, Emmanuel JOVER, Gilles PREVOST) Collection Rencontres en Toxinologie La collection « Rencontres en Toxinologie » est publiée à l’occasion des Colloques annuels « Rencontres en Toxinologie » organisés par la Société Française pour l’Etude des Toxines (SFET).
    [Show full text]
  • Research on the Alkaloids of Amaryllidaceae Plants: Genera Lycoris and Hippeastrum
    Research on the Alkaloids of Amaryllidaceae Plants: Genera Lycoris and Hippeastrum Ying Guo ADVERTIMENT . La consulta d’aquesta tesi queda condicionada a l’acceptació de les següents condicions d'ús: La difusió d’aquesta tesi per mitjà del servei TDX ( www.tdx.cat ) i a través del Dipòsit Digital de la UB ( diposit.ub.edu ) ha estat autoritzada pels titulars dels drets de propietat intel·lectual únicament per a usos privats emmarcats en a ctivitats d’investigació i docència. No s’autoritza la seva reproducció amb finalitats de lucre ni la seva difusió i posada a disposici ó des d’un lloc aliè al servei TDX ni al Dipòsit Digital de la UB . No s’autoritza la presentació del seu contingut en una finestra o marc aliè a TDX o al Dipòsit Digital de la UB (framing). Aquesta reserva de drets afecta tant al resum de presentació de la tesi com als seus continguts. En la utilització o cita de parts de la tesi és obligat indicar el nom de la persona autor a. ADVERTENCIA . La consulta de esta tesis queda condicionada a la aceptación de las siguientes condiciones de uso: La difusión de esta tesis por medio del servicio TDR ( www.tdx.cat ) y a través del Repositorio Digital de la UB ( diposit.ub.edu ) ha sido autorizada por los titulares de los derechos de propiedad intelectual únicamente para usos privados enmarcados en actividades de investigación y docencia. No se autoriza su reproducción con finalidades de lucro ni su difusión y puesta a disposición desde u n sitio ajeno al servicio TDR o al Repositorio Digital de la UB .
    [Show full text]
  • Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Epilepsy
    Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Epilepsy Chemical Activity Count (+)-ALPHA-VINIFERIN 1 (+)-BORNYL-ISOVALERATE 1 (+)-CATECHIN 3 (+)-EUDESMA-4(14),7(11)-DIENE-3-ONE 1 (+)-HERNANDEZINE 1 (+)-ISOCORYDINE 1 (+)-PSEUDOEPHEDRINE 1 (+)-SYRINGARESINOL-DI-O-BETA-D-GLUCOSIDE 1 (+)-T-CADINOL 1 (-)-16,17-DIHYDROXY-16BETA-KAURAN-19-OIC 1 (-)-ALPHA-BISABOLOL 2 (-)-ANABASINE 1 (-)-APOGLAZIOVINE 1 (-)-BETONICINE 1 (-)-BORNYL-CAFFEATE 1 (-)-BORNYL-FERULATE 1 (-)-BORNYL-P-COUMARATE 1 (-)-DICENTRINE 2 (-)-EPIAFZELECHIN 1 (-)-EPICATECHIN 1 (-)-EPIGALLOCATECHIN-GALLATE 1 (1'S)-1'-ACETOXYCHAVICOL-ACETATE 1 (15:1)-CARDANOL 1 (E)-4-(3',4'-DIMETHOXYPHENYL)-BUT-3-EN-OL 1 1,7-BIS-(4-HYDROXYPHENYL)-1,4,6-HEPTATRIEN-3-ONE 1 1,8-CINEOLE 4 10-ACETOXY-8-HYDROXY-9-ISOBUTYLOXY-6-METHOXYTHYMOL 1 Chemical Activity Count 10-DEHYDROGINGERDIONE 1 10-GINGERDIONE 1 11-HYDROXY-DELTA-8-THC 1 11-HYDROXY-DELTA-9-THC 1 13',II8-BIAPIGENIN 1 13-OXYINGENOL-ESTER 1 16,17-DIHYDROXY-16BETA-KAURAN-19-OIC 1 16-EPIMETHUENINE 1 16-HYDROXYINGENOL-ESTER 1 2'-O-GLYCOSYLVITEXIN 1 2-BETA,3BETA-27-TRIHYDROXYOLEAN-12-ENE-23,28-DICARBOXYLIC-ACID 1 2-METHYLBUT-3-ENE-2-OL 2 20-DEOXYINGENOL-ESTER 1 22BETA-ESCIN 1 24-METHYLENE-CYCLOARTANOL 1 3,3'-DIMETHYLELLAGIC-ACID 1 3,4-DIMETHOXYTOLUENE 1 3,4-METHYLENE-DIOXYCINNAMIC-ACID-BORNYL-ESTER 2 3,4-SECOTRITERPENE-ACID-20-EPI-KOETJAPIC-ACID 1 3-ACETYLACONITINE 1 3-ACETYLNERBOWDINE 1 3-BETA-HYDROXY-2,3-DIHYDROWITHANOLIDE-F 1 3-HYDROXY-FLAVONE 1 3-N-BUTYL-PHTHALIDE 3 3-O-ACETYLOLEANOLIC-ACID 1 3-OXO-11-ALPHA-HYDROXYOLEAN-12-ENE-30-OIC-ACID
    [Show full text]
  • The Steric Factor in Medicinal Chemistry
    The Steric Factor in Medicinal Chemistry Dissymmetrie Pro bes of Pharmacological Receptors The Steric Factor in Medicinal Chetnistry Dissymmetrie Pro bes of Pharmacological Receptors Alan F. easy University 0/ Bath Bath, United Kingdom With a contribution by George H. Dewar University 0/ Bath Bath, United Kingdom Springer Science+Business Media, LLC llbrary of Congress CataJoglng-ln-PubJlcatlon Data Casy, Alan F. The steric factor In Medlclnal cheMlstry , dlssYM.etrlc probes of pharMacological receptors / Alan F. Casy ; wlth a contributlon by George H. Dewar. p. c •. Includes bibllographlcal references and Index. 1. Drugs--Structure-actlvlty relatlonshlps. 2. Drug receptors. 3. Stereochemistry. I. Dewar, George H. 11. Tltle. RM301.42.C37 1993 615' .7--dc20 93-6290 CIP ISBN 978-1-4899-2399-8 ISBN 978-1-4899-2397-4 (eBook) DOI 10.1007/978-1-4899-2397-4 © 1993 Springer Science+Business Media New York Originally published by Plenum Press, New York in 1993. Softcover reprint of the hardcover 1st edition 1993 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher With love 10 my wife, M ary Foreword Stereochemistry was born in the second half of the 19th century with the publica­ tions of Pasteur in 1860, van't Hoff in 1874, and Le Bel in 1874, a remarkable period that followed rather closely the progressive appearance of chemistry as we understand it now. But chemical compounds are three-dimensional entities, implying that, in so me sense, the whole of chemistry is stereochemistry.
    [Show full text]
  • Screening and in Silico Analysis of Hyptis Suaveolens Metabolites for Acetylcholinesterase Inhibition
    Online - 2455-3891 Vol 9, Issue 3, 2016 Print - 0974-2441 Research Article SCREENING AND IN SILICO ANALYSIS OF HYPTIS SUAVEOLENS METABOLITES FOR ACETYLCHOLINESTERASE INHIBITION VBSC THUNUGUNTLA1, CHANDRA SEKHAR B1, KALA KUMAR B2, BONDILI JS1* 1Department of Biotechnology, K L University, Greenfields, Vaddeswaram, Guntur - 522 502, Andhra Pradesh, India. 2Department of Pharmacology and Toxicology, College of Veterinary Science, Hyderabad, Telangana, India. *Email: [email protected] Received: 19 January 2016, Revised and Accepted: 26 January 2016 ABSTRACT Objective: Current drugs to Alzheimer’s disease (AD) are targeted to delay the breakdown of acetylcholine, thereby increasing the concentration of acetylcholine released into synaptic cleft and enhancing cholinergic neurotransmission. This paper deals with screening and identification of acetylcholinesterase (AChE) inhibitors in solvent extracts of Hyptis suaveolens (HS). Methods: In search of natural inhibitors of AChE, this study is focused on extract of HS, a member of Lamiaceae. 1:4 ratio of methanolic extract is prepared with shade dried areal parts of HS plant. The extract was assayed by Ellman’s method for inhibition activity and then purified using ammonium sulfate precipitation and chromatography techniques. Gas chromatography-mass spectrometry (GC-MS) identified compounds were analyzed by docking studies. Results: Methanolic extract showed maximum percentage inhibition of 75.00±4.30 (2.1 mg/ml) with an IC50 value of 1.020±0.026 mg/ml. However, saturated ammonium sulfate precipitation of methanolic extract and further fractionation by gel permeation chromatography showed 86.00±1.30% AChE inhibition (AChEI) activity. Reverse phase high-performance liquid chromatography (RP-HPLC) fraction (retention time [RT] 5.170) showed significant inhibition when compared to the other peak (RT 6.643).
    [Show full text]