{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T23:02:59Z","timestamp":1774047779446,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:00:00Z","timestamp":1690502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009307","name":"Parkinson Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009307","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012479","name":"Weston Brain Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000155","name":"Social Sciences and Humanities Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nelotanserin is a serotonin 2A and 2C (5\u2010HT<jats:sub>2A\/2C<\/jats:sub>) inverse agonist that was previously tested in the clinic for rapid\u2010eye movement sleep behaviour disorder and psychosis in patients with Parkinson's disease (PD) dementia. Its effect on L\u20103,4\u2010dihydroxyphenylalanine (L\u2010DOPA)\u2010induced dyskinesia has however not been investigated. As 5\u2010HT<jats:sub>2A<\/jats:sub> antagonism\/inverse agonism is a validated approach to alleviate dyskinesia, we undertook the current study to evaluate the anti\u2010dyskinetic potential of nelotanserin in the 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP)\u2010lesioned marmoset. Parkinsonism was induced in six common marmosets (<jats:styled-content style=\"fixed-case\"><jats:italic>Callithrix jacchus<\/jats:italic><\/jats:styled-content>, three females and three males) that were then chronically treated with L\u2010DOPA to induce dyskinesia. On experimental days, they were administered L\u2010DOPA in combination with vehicle or nelotanserin (0.1, 0.3 and 1\u00a0mg\/kg) subcutaneously, in a randomised fashion. Dyskinesia and parkinsonism were rated post hoc by a blinded observer. In comparison to vehicle, the addition of nelotanserin 0.3 and 1\u00a0mg\/kg to L\u2010DOPA diminished peak dose dyskinesia by 47% (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) and 69% (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Nelotanserin 0.3 and 1\u00a0mg\/kg also reduced the severity of global dyskinesia, by 40% (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01) and 55% (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), when compared to vehicle. Nelotanserin 0.1\u00a0mg\/kg did not alleviate peak dose or global dyskinesia severity. Nelotanserin had no impact on the anti\u2010parkinsonian action of L\u2010DOPA. Our results highlight that nelotanserin may represent an efficacious anti\u2010dyskinetic drug and provide incremental evidence of the potential benefit of 5\u2010HT<jats:sub>2A\/2C<\/jats:sub> antagonism\/inverse agonism for drug\u2010induced dyskinesia in PD.<\/jats:p>","DOI":"10.1111\/ejn.16104","type":"journal-article","created":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T05:35:36Z","timestamp":1690608936000},"page":"1169-1176","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The 5\u2010HT<sub>2A\/2C<\/sub> inverse agonist nelotanserin alleviates L\u2010DOPA\u2010induced dyskinesia in the MPTP\u2010lesioned marmoset"],"prefix":"10.1111","volume":"59","author":[{"given":"Cynthia","family":"Kwan","sequence":"first","affiliation":[{"name":"Neurodegenerative Disease Group Montreal Neurological Institute\u2010Hospital (The Neuro)  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imane","family":"Frouni","sequence":"additional","affiliation":[{"name":"Neurodegenerative Disease Group Montreal Neurological Institute\u2010Hospital (The Neuro)  Montreal Quebec Canada"},{"name":"D\u00e9partement de Pharmacologie et Physiologie Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"B\u00e9dard","sequence":"additional","affiliation":[{"name":"Neurodegenerative Disease Group Montreal Neurological Institute\u2010Hospital (The Neuro)  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9869-6752","authenticated-orcid":false,"given":"Adjia","family":"Hamadjida","sequence":"additional","affiliation":[{"name":"Neurodegenerative Disease Group Montreal Neurological Institute\u2010Hospital (The Neuro)  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen G.","family":"Nuara","sequence":"additional","affiliation":[{"name":"Comparative Medicine &amp; Animal Resource Centre McGill University  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jim C.","family":"Gourdon","sequence":"additional","affiliation":[{"name":"Comparative Medicine &amp; Animal Resource Centre McGill University  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5464-8334","authenticated-orcid":false,"given":"Philippe","family":"Huot","sequence":"additional","affiliation":[{"name":"Neurodegenerative Disease Group Montreal Neurological Institute\u2010Hospital (The Neuro)  Montreal Quebec Canada"},{"name":"D\u00e9partement de Pharmacologie et Physiologie Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"},{"name":"Department of Neurology and Neurosurgery McGill University  Montreal Quebec Canada"},{"name":"Movement Disorder Clinic, Division of Neurology, Department of Neurosciences McGill University Health Centre  Montreal QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,7,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.160994"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199307153290303"},{"key":"e_1_2_10_4_1","unstructured":"Axovant Sciences Ltd Therapies SG. 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