{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:06:24Z","timestamp":1790827584492,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,3,21]],"date-time":"2020-03-21T00:00:00Z","timestamp":1584748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"IRLAB"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>IRL752 is a novel small\u2010molecule compound that acts to regioselectively enhance norepinephrine, dopamine, and acetylcholine neurotransmission in the cerebral cortex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The primary objective of the trial was to investigate the safety and tolerability of IRL752 in patients with Parkinson's disease and dementia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with Parkinson's disease and dementia were randomized to IRL752 or placebo treatment (3:1 ratio) for 28\u2009days. The study drug was given as an adjunct treatment to the patients\u2019 regular stable antiparkinsonian medication. Dosing was individually titrated for 14\u2009days after which the dose was kept stable for an additional 14\u2009days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 32 patients were randomized to treatment, and 29 patients completed the 4\u2010week treatment. Adverse events were generally mild and transient and were mostly reported during the dose titration phase. There were 2 serious adverse events, and none of them were related to the experimental treatment. The average dose achieved in the stable dose phase was 600 mg daily, yielding a 2\u2010hour postdose plasma concentration of about 4 \u03bcM on day 28. Exploratory assessment of secondary outcomes indicated efficacy for symptoms and signs known to be poorly responsive to levodopa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>IRL752 appears to be safe and well tolerated for a 4\u2010week treatment in patients with Parkinson's disease and dementia. \u00a9 2020 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28020","type":"journal-article","created":{"date-parts":[[2020,3,21]],"date-time":"2020-03-21T04:59:21Z","timestamp":1584766761000},"page":"1046-1054","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson's Disease Dementia"],"prefix":"10.1002","volume":"35","author":[{"given":"Per","family":"Svenningsson","sequence":"first","affiliation":[{"name":"Section of Neurology, Department of Clinical Neuroscience Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Odin","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Clinical Sciences Lund Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nil","family":"Dizdar","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Johansson","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Clinical Neuroscience Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotirios","family":"Grigoriou","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Clinical Sciences Lund Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiota","family":"Tsitsi","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Clinical Neuroscience Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klas","family":"Wictorin","sequence":"additional","affiliation":[{"name":"Department of Neurology Helsingborg Hospital  Helsingborg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Bergquist","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dag","family":"Nyholm","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Neurology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Rinne","sequence":"additional","affiliation":[{"name":"Clinical Research Services Turku Oy  Turku Finland"},{"name":"Division of Clinical Neurosciences Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Hansson","sequence":"additional","affiliation":[{"name":"Clinical Trial Consultants  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clas","family":"Sonesson","sequence":"additional","affiliation":[{"name":"Integrative Research Laboratories AB  G\u00f6teborg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joakim","family":"Tedroff","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Clinical Neuroscience Karolinska Institutet  Stockholm Sweden"},{"name":"Integrative Research Laboratories AB  G\u00f6teborg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the IRL752 Collaborators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20834"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61393-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21956"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70152-7"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-198908000-00006"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-6362(00)00076-X"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.01044"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-004-0956-9"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.246"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00389-0"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70106-0"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.6b00371"},{"key":"e_1_2_9_14_1","volume-title":"Paper presented at: Society for Neuroscience","author":"Waters S","year":"2019"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1353-8020(99)00062-0"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.1991.tb01616.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.12.2308"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/089198879600900404"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1982.0082"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3932(90)90137-D"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-0643-3_11"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.9.2.279"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25857"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000218"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/115.6.1727"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp245"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02245167"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21507"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmds.28020","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.28020","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.28020","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.28020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T11:50:08Z","timestamp":1760961008000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.28020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,21]]},"references-count":27,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1002\/mds.28020"],"URL":"https:\/\/doi.org\/10.1002\/mds.28020","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,21]]},"assertion":[{"value":"2019-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}