{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:07:56Z","timestamp":1773306476813,"version":"3.50.1"},"reference-count":59,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,3,30]],"date-time":"2017-03-30T00:00:00Z","timestamp":1490832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"The Michael J. Fox Foundation for Parkinson's Research to Avanir Pharmaceuticals, Inc"},{"DOI":"10.13039\/100014934","name":"Avanir Pharmaceuticals, Inc","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014934","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:bold>Background<\/jats:bold>: Nondopaminergic pathways represent potential targets to treat levodopa\u2010induced dyskinesia in Parkinson's disease (PD). This pilot\u2010study (NCT01767129) examined the safety\/efficacy of the sigma\u20101 receptor\u2010agonist and glutamatergic\/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa\u2010induced dyskinesia.<\/jats:p><jats:p><jats:bold>Methods<\/jats:bold>: PD patients were randomized to dextromethorphan\/quinidine (45\u2009mg\/10\u2009mg twice daily)\/placebo in two 2\u2010week double\u2010blind, crossover treatment periods, with intervening 2\u2010week washout. After 14 days, a 2\u2010hour intravenous levodopa\u2010infusion was administered. Patient examinations were videotaped before infusion (\u201coff\u201d state) and every 30 minutes during and afterwards until patients returned to \u201coff.\u201d The primary endpoint was dyskinesia\u2010severity during infusion measured by Unified Dyskinesia Rating Scale part 3 area\u2010under\u2010curve scores (blinded expert rated). Additional endpoints included other dyskinesia\/motor assessments, global measures of clinical\u2010change, and adverse\u2010events.<\/jats:p><jats:p><jats:bold>Results<\/jats:bold>: A total of 13 patients were randomized and completed the study (efficacy\u2010evaluable population). Dyskinesia\u2010severity was nonsignificantly lower with dextromethorphan\/quinidine than placebo during infusion (area\u2010under\u2010curve 966.5 vs 1048.8; <jats:italic>P<\/jats:italic>\u2009=\u2009.191 [efficacy\u2010evaluable patients]), and significantly lower in a post\u2010hoc sensitivity analysis of the per\u2010protocol\u2010population (efficacy\u2010evaluable patients with\u2009\u2265\u200980% study\u2010drug\u2010compliance, n\u2009=\u200912) when measured from infusion start to 4\u2010hours post\u2013infusion completion (area\u2010under\u2010curve 1585.0 vs 1911.3; <jats:italic>P<\/jats:italic>\u2009=\u2009.024). Mean peak dyskinesia decreased significantly from infusion\u2010start to return to \u201coff\u201d (13.3 vs 14.9; <jats:italic>P<\/jats:italic>\u2009=\u2009.018 [efficacy\u2010evaluable patients]). A total of 9 patients rated dyskinesia \u201cmuch\/very much improved\u201d on dextromethorphan\/quinidine versus 1\u2010patient on placebo. Dextromethorphan\/quinidine did not worsen PD\u2010motor scores, was generally well tolerated, and was associated with more frequent adverse events.<\/jats:p><jats:p><jats:bold>Conclusion<\/jats:bold>: This study provides preliminary evidence of clinical benefit with dextromethorphan\/quinidine for treating levodopa\u2010induced dyskinesia in PD. Larger studies with a longer treatment duration need to corroborate these early findings. \u00a9 2017 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.26976","type":"journal-article","created":{"date-parts":[[2017,3,30]],"date-time":"2017-03-30T14:45:40Z","timestamp":1490885140000},"page":"893-903","source":"Crossref","is-referenced-by-count":35,"title":["Trial of dextromethorphan\/quinidine to treat levodopa\u2010induced dyskinesia in Parkinson's disease"],"prefix":"10.1002","volume":"32","author":[{"given":"Susan H.","family":"Fox","sequence":"first","affiliation":[{"name":"The Edmond J Safra Program in Parkinson's Disease University Health Network, Toronto Western Hospital Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard Verhagen","family":"Metman","sequence":"additional","affiliation":[{"name":"Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John G.","family":"Nutt","sequence":"additional","affiliation":[{"name":"Oregon Health and Science University Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Brodsky","sequence":"additional","affiliation":[{"name":"Oregon Health and Science University Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stewart A.","family":"Factor","sequence":"additional","affiliation":[{"name":"Emory University Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony E.","family":"Lang","sequence":"additional","affiliation":[{"name":"The Edmond J Safra Program in Parkinson's Disease University Health Network, Toronto Western Hospital Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura E.","family":"Pope","sequence":"additional","affiliation":[{"name":"Avanir Pharmaceuticals, Inc Aliso Viejo California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"Knowles","sequence":"additional","affiliation":[{"name":"Avanir Pharmaceuticals, Inc Aliso Viejo California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o","family":"Siffert","sequence":"additional","affiliation":[{"name":"Avanir Pharmaceuticals, Inc Aliso Viejo California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005183422004"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21743"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2005.01096.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008928321652"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00019053-200119100-00004"},{"key":"e_1_2_8_7_1","first-page":"1605","article-title":"Levodopa\u2010induced dyskinesias in Parkinson's disease: emerging treatments","volume":"9","author":"Bargiotas P","year":"2013","journal-title":"Neuropsychiatr Dis Treat"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-011-0698-2"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70218-0"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2471"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900802106"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00007759"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr028"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20936"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-009-1505-8"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm082"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2007.01.013"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22473"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21475"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21226"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2009.07.001"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.2174\/157015908787386113"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0953-816X.2004.03297.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704294"},{"issue":"2","key":"e_1_2_8_25_1","first-page":"CD003467","article-title":"Amantadine for dyskinesia in Parkinson's disease","author":"Crosby NJ","year":"2003","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870130507"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2012.08243.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.5.1323"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.1112"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23034"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015298"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2004.036558"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26159"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(87)90070-9"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(93)90849-D"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91474-F"},{"issue":"1","key":"e_1_2_8_37_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0026-895X(25)10081-3","article-title":"Effects of dextromethorphan site ligands and allosteric modifiers on the binding of (+)\u2010[3H]3\u2010(\u20103\u2010hydroxyphenyl)\u2010N\u2010(1\u2010propyl)piperidine","volume":"35","author":"Musacchio JM","year":"1989","journal-title":"Mol Pharmacol"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)91144-4"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.06.013"},{"issue":"3","key":"e_1_2_8_40_1","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/S0022-3565(25)10630-7","article-title":"Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception","volume":"274","author":"Codd EE","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.075093"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00558166"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015835215945"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-199508000-00005"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270004269521"},{"key":"e_1_2_8_46_1","volume-title":"Dextromethorphan hydrobromide and quinidine sulfate capsules [package insert]","author":"NUEDEXTA","year":"2010"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870130307"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.51.1.203"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNF.0b013e31823d78c4"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.09.044"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23429"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22341"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21198"},{"issue":"14","key":"e_1_2_8_54_1","first-page":"153","article-title":"Objective measurement of upper extremity motor function in the Parkinson's Progression Marker Initiative","volume":"84","author":"Chahine L","year":"2015","journal-title":"Neurology"},{"key":"e_1_2_8_55_1","unstructured":"Objective Parkinson's Disease Measurement (OPDM) System. Kinetics Foundation San Francisco USA.www.kineticsfoundation.org."},{"issue":"4","key":"e_1_2_8_56_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1023\/A:1008979705027","article-title":"Quality of life and Parkinson's disease: translation and validation of the US Parkinson's Disease Questionnaire (PDQ\u201039)","volume":"8","author":"Bushnell DM","year":"1999","journal-title":"Qual Life Res"},{"key":"e_1_2_8_57_1","volume-title":"ECDEU Assessment Manual for Psychopharmacology","author":"Guy W","year":"1976"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-200003000-00003"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2011.10111704"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.53221.x"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmds.26976","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.26976","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:24:05Z","timestamp":1760955845000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.26976"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,30]]},"references-count":59,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1002\/mds.26976"],"URL":"https:\/\/doi.org\/10.1002\/mds.26976","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,30]]}}}