{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:43:54Z","timestamp":1772160234068,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"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\/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\/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\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","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":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Activation of metabotropic glutamate 2 (mGlu\n                    <jats:sub>2<\/jats:sub>\n                    ) receptors is a potential novel therapeutic approach for the treatment of parkinsonism. Thus, when administered as monotherapy or as adjunct to a low dose of L\u20103,4\u2010dihydroxyphenylalanine (L\u2010DOPA), the mGlu\n                    <jats:sub>2<\/jats:sub>\n                    positive allosteric modulator (PAM) LY\u2010487,379 alleviated parkinsonism in 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP)\u2010lesioned primates. Here, we sought to investigate the effect of biphenyl\u2010indanone A (BINA), a highly selective mGlu\n                    <jats:sub>2<\/jats:sub>\n                    PAM whose chemical scaffold is unrelated to LY\u2010487,379, to determine if a structurally different mGlu\n                    <jats:sub>2<\/jats:sub>\n                    PAM would also confer anti\u2010parkinsonian benefit. In monotherapy experiments, MPTP\u2010lesioned marmosets were injected with either vehicle, L\u2010DOPA\/benserazide (15\/3.75\u2009mg\/kg, positive control) or BINA (0.1, 1, 10\u00a0mg\/kg). In adjunct to a low L\u2010DOPA dose experiments, MPTP\u2010lesioned marmosets were injected with L\u2010DOPA\/benserazide (7.5\/1.875\u2009mg\/kg) in combination with vehicle or BINA (0.1, 1, 10\u00a0mg\/kg). Parkinsonism, dyskinesia and psychosis\u2010like behaviours (PLBs) were then quantified. When administered alone, BINA 1 and 10\u00a0mg\/kg decreased parkinsonism severity by ~22% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01) and ~47% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), when compared with vehicle, which was comparable with the global effect of a high L\u2010DOPA dose. When administered in combination with a low L\u2010DOPA dose, BINA 1 and 10\u00a0mg\/kg decreased global parkinsonism by ~38% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and ~53% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). BINA 10\u00a0mg\/kg decreased global dyskinesia by ~94% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01) and global PLBs by ~92% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). Our results provide additional evidence that mGlu\n                    <jats:sub>2<\/jats:sub>\n                    positive allosteric modulation elicits anti\u2010parkinsonian effects. That this benefit is not related to a particular chemical scaffold suggests that it may be a class effect rather than the effect of a specific molecule.\n                  <\/jats:p>","DOI":"10.1111\/ejn.16454","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T19:55:09Z","timestamp":1719518109000},"page":"6175-6184","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effect of the mGlu\n                    <sub>2<\/sub>\n                    positive allosteric modulator biphenyl\u2010indanone A as a monotherapy and as adjunct to a low dose of L\u2010DOPA in the MPTP\u2010lesioned marmoset"],"prefix":"10.1111","volume":"60","author":[{"given":"Woojin","family":"Kang","sequence":"first","affiliation":[{"name":"Neurodegenerative Disorders Research Group Montreal Neurological Institute\u2010Hospital (The Neuro)  Montreal QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imane","family":"Frouni","sequence":"additional","affiliation":[{"name":"Neurodegenerative Disorders Research Group Montreal Neurological Institute\u2010Hospital (The Neuro)  Montreal QC Canada"},{"name":"D\u00e9partement de Pharmacologie et Physiologie Universit\u00e9 de Montr\u00e9al  Montreal QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia","family":"Kwan","sequence":"additional","affiliation":[{"name":"Neurodegenerative Disorders Research Group Montreal Neurological Institute\u2010Hospital (The Neuro)  Montreal QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"B\u00e9dard","sequence":"additional","affiliation":[{"name":"Neurodegenerative Disorders Research Group Montreal Neurological Institute\u2010Hospital (The Neuro)  Montreal QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen G.","family":"Nuara","sequence":"additional","affiliation":[{"name":"Comparative Medicine &amp; Animal Resource Centre McGill University  Montreal QC 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 Disorders Research Group Montreal Neurological Institute\u2010Hospital (The Neuro)  Montreal QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jim C.","family":"Gourdon","sequence":"additional","affiliation":[{"name":"Comparative Medicine &amp; Animal Resource Centre McGill University  Montreal QC 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 Disorders Research Group Montreal Neurological Institute\u2010Hospital (The Neuro)  Montreal QC Canada"},{"name":"D\u00e9partement de Pharmacologie et Physiologie Universit\u00e9 de Montr\u00e9al  Montreal QC Canada"},{"name":"Department of Neurology and Neurosurgery McGill University  Montreal QC Canada"},{"name":"Department of Neurosciences McGill University Health Centre  Montreal QC 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