{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T23:19:23Z","timestamp":1794352763904,"version":"4.9.0"},"reference-count":84,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:00:00Z","timestamp":1607385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a common neurodegenerative disorder that leads to significant morbidity and disability. PD is caused by a loss of dopaminergic, cholinergic, serotonergic, and noradrenergic neurons in the central nervous system (CNS), and peripherally; the syndromic parkinsonism symptoms of movement disorder, gait disorder, rigidity and tremor are mostly driven by the loss of these neurons in the basal ganglia. Unfortunately, a significant proportion of patients taking levodopa, the standard of care treatment for PD, will begin to experience a decrease in effectiveness at varying times. These periods, referred to as \u201coff episodes\u201d, are characterized by increased symptoms and have a detrimental effect on quality of life and disability. Istradefylline, a novel adenosine A2A receptor antagonist, is indicated as a treatment addition to levodopa\/carbidopa in patients experiencing \u201coff episodes\u201d. It promotes dopaminergic activity by antagonizing adenosine in the basal ganglia. This review will discuss istradefylline as a treatment for PD patients with off episodes.<\/jats:p>","DOI":"10.3390\/neurolint12030017","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T22:15:36Z","timestamp":1607638536000},"page":"109-129","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Istradefylline to Treat Patients with Parkinson\u2019s Disease Experiencing \u201cOff\u201d Episodes: A Comprehensive Review"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7895-1357","authenticated-orcid":false,"given":"Amnon A.","family":"Berger","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1675-5446","authenticated-orcid":false,"given":"Ariel","family":"Winnick","sequence":"additional","affiliation":[{"name":"Soroka University Medical Center and Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva 8410501, Israel"},{"name":"School of Optometry, University of California, Berkeley, CA 94704, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0158-3995","authenticated-orcid":false,"given":"Alexandra","family":"Welschmeyer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Georgetown University School of Medicine, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Kaneb","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Georgetown University School of Medicine, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Berardino","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Georgetown University School of Medicine, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyse M.","family":"Cornett","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, LSU Health Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan D.","family":"Kaye","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, LSU Health Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Viswanath","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, LSU Health Shreveport, Shreveport, LA 71103, USA"},{"name":"Department of Anesthesiology, University of Arizona College of Medicine\u2014Phoenix, Phoenix, AZ 85004, USA"},{"name":"Department of Anesthesiology, Creighton University School of Medicine, Omaha, NE 68124, USA"},{"name":"Valley Anesthesiology and Pain Consultants\u2014Envision Physician Services, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Urits","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, LSU Health Shreveport, Shreveport, LA 71103, USA"},{"name":"Southcoast Health, Southcoast Physicians Group Pain Medicine, Wareham, MA 02571, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S1474-4422(06)70471-9","article-title":"Epidemiology of Parkinson\u2019s disease","volume":"5","author":"Breteler","year":"2006","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/S1474-4422(18)30295-3","article-title":"Global, regional, and national burden of Parkinson\u2019s disease, 1990\u20132016: A systematic analysis for the global burden of disease study 2016","volume":"17","author":"Elbaz","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s40265-020-01310-2","article-title":"Therapeutic strategies to treat or prevent off episodes in adults with Parkinson\u2019s Disease","volume":"80","author":"Vijiaratnam","year":"2020","journal-title":"Drugs"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/S1474-4422(16)30230-7","article-title":"The epidemiology of Parkinson\u2019s disease: Risk factors and prevention","volume":"15","author":"Ascherio","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1002\/mds.25945","article-title":"The prevalence of Parkinson\u2019s disease: A systematic review and meta-analysis","volume":"29","author":"Pringsheim","year":"2014","journal-title":"Mov. 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