{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:45:43Z","timestamp":1790793943997,"version":"4.1.0"},"reference-count":9,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,5,23]],"date-time":"2016-05-23T00:00:00Z","timestamp":1463961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Addex Pharma SA"},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The metabotropic glutamate receptor 5\u2010negative allosteric modulator dipraglurant reduces levodopa\u2010induced dyskinesia in the MPTP\u2010macaque model. The objective of this study was to assess the safety, tolerability (primary objective), and efficacy (secondary objective) of dipraglurant on levodopa\u2010induced dyskinesia in Parkinson's disease (PD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study was a phase\u00a02A double\u2010blind, placebo\u2010controlled, randomized (2:1), 4\u2010week, parallel\u2010group, multicenter dose\u2010escalation (from 50 mg once daily to 100 mg 3 times daily) clinical trial involving 76 PD subjects with moderate to severe levodopa\u2010induced dyskinesia. Safety and tolerability were assessed based on clinical and biological examination and adverse events recording. Secondary efficacy outcome measures included the modified Abnormal Involuntary Movement Scale, UPDRS, and diaries. Pharmacokinetics were measured at 3 visits following a single dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty\u2010two patients were exposed to dipraglurant and 24 to placebo. There were no major safety concerns. Two subjects did not complete the study because of adverse events. Most frequent adverse events included dyskinesia, dizziness, nausea, and fatigue. Dipraglurant significantly reduced peak dose dyskinesia (modified Abnormal Involuntary Movement Scale) on day 1 (50 mg, 20%;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.04) and on day 14 (100 mg, 32%;\n                      <jats:italic>P<\/jats:italic>\n                      =0 .04) and across a 3\u2010hour postdose period on day 14 (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.04). There was no evidence of worsening of parkinsonism. Dipraglurant was rapidly absorbed (t\n                      <jats:sub>max<\/jats:sub>\n                      = 1 hour). The 100\u2010mg dose led to a mean C\n                      <jats:sub>max<\/jats:sub>\n                      of 1844 ng\/mL on day 28.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dipraglurant proved to be safe and well tolerated in its first administration to PD patients. Its efficacy in reversing levodopa\u2010induced dyskinesia warrants further investigations in a larger number of patients. \u00a9 2016 International Parkinson and Movement Disorder Society<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.26659","type":"journal-article","created":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T06:38:14Z","timestamp":1464071894000},"page":"1373-1380","source":"Crossref","is-referenced-by-count":134,"title":["A Phase 2A Trial of the Novel mGluR5\u2010Negative Allosteric Modulator Dipraglurant for Levodopa\u2010Induced Dyskinesia in Parkinson's Disease"],"prefix":"10.1002","volume":"31","author":[{"given":"Fran\u00e7ois","family":"Tison","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Bordeaux, Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives Bordeaux France"},{"name":"CNRS, Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives UMR 5293 Bordeaux France"},{"name":"Service de Neurologie CHU de Bordeaux Bordeaux France"},{"name":"NS\u2010Park\/FCRIN Network UMS 015 Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Keywood","sequence":"additional","affiliation":[{"name":"Addex Pharma SA Plan Les Ouates Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Wakefield","sequence":"additional","affiliation":[{"name":"Addex Pharma SA Plan Les Ouates Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Durif","sequence":"additional","affiliation":[{"name":"NS\u2010Park\/FCRIN Network UMS 015 Toulouse France"},{"name":"Neurology Service, A H\u00f4pital Gabriel Montpied Clermont Ferrand France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Christophe","family":"Corvol","sequence":"additional","affiliation":[{"name":"NS\u2010Park\/FCRIN Network UMS 015 Toulouse France"},{"name":"Sorbonne Universit\u00e9s and UPMC Univ Paris 06, INSERM UMRS\u20101127 and CIC\u20101422; CNRS UMR\u20107225; AP\u2010HP; and ICM, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Eggert","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Giessen und Marburg, Klinik f\u00fcr Neurologie Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Lew","sequence":"additional","affiliation":[{"name":"Department of Neurology USC\/Keck School of Medicine Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Isaacson","sequence":"additional","affiliation":[{"name":"Parkinson's Disease and Movement Disorders Center of Boca Raton Boca Raton Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwan","family":"Bezard","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux, Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives Bordeaux France"},{"name":"CNRS, Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives UMR 5293 Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia\u2010Maria","family":"Poli","sequence":"additional","affiliation":[{"name":"Addex Pharma SA Plan Les Ouates Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G.","family":"Goetz","sequence":"additional","affiliation":[{"name":"Rush University Medical Center, Dept. of Neurological Sciences, Movement Disorder Section Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Trenkwalder","sequence":"additional","affiliation":[{"name":"Paracelsus Elena Klinik, centre for Parkinson's Disease &amp; Movement Disorders Kassel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Rascol","sequence":"additional","affiliation":[{"name":"NS\u2010Park\/FCRIN Network UMS 015 Toulouse France"},{"name":"CIC9302, Departments of Clinical Pharmacology and Neurosciences and NeuroToul COEN Center; INSERM University Hospital of Toulouse and University of Toulouse 3 Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,23]]},"reference":[{"issue":"1","key":"e_1_2_9_2_1","first-page":"S179","article-title":"Medical treatment of levodopa\u2010induced dyskinesias","volume":"47","author":"Rascol O","year":"2000","journal-title":"Ann Neurol"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2005.01096.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23829"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-381328-2.00004-3"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2014.05.003"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25920"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25561"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25321"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/157488407781668802"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmds.26659","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmds.26659","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.26659","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T11:14:01Z","timestamp":1760958841000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.26659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,23]]},"references-count":9,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["10.1002\/mds.26659"],"URL":"https:\/\/doi.org\/10.1002\/mds.26659","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.726375502.793520446","asserted-by":"object"}]},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,23]]}}}