{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T08:08:03Z","timestamp":1774512483559,"version":"3.50.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The standard therapy of Parkinson\u2019s disease consists in supplementing the depleted dopamine with oral levodopa. The disadvantages of the levodopa monotherapy \u2013 comparable to other dopaminergic substances \u2013 are the dose-dependent development of dyskinesia in ON-phases, and bradykinesia and akinesia in OFF-phases, the latter being a sign of dopaminergic deficiency with a recurrence of Parkinson\u2019s symptoms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim of the study<\/jats:title>\n                    <jats:p>In order to omit the side effects of levodopa, we devised a combination therapy consisting of amantadine, a monoamine oxidase type B-inhibitor and a dopamine agonist. Levodopa was added at a low dose, if necessary.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a retrospective, monocenter study based on the patient records, we report the long-term results in 132 PD patients who had been treated with the amantadine-based therapy for up to 13\u202fyears in an outpatient Parkinson clinic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In 132 patients with the amantadine-based combination therapy, the mean UPDRS III score improved by 5.7 points from baseline during the first 2\u202fyears of treatment. Over the following 3 years it increased and remained at a plateau level slightly below baseline for the next 5\u202fyears. At no time did more than 20% of the patients suffer from Hoehn &amp;amp; Yahr stage 3 or higher. Only seven patients exhibited \u201cOFF\u201d periods and only seven (6 with additional levodopa) presented with dyskinesia at any time during therapy. The most important adverse effect was lower leg edema.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The combination therapy of amantadine, a monoamine oxidase type B-inhibitor and a dopamine agonist is an alternate therapeutic approach that may be able to prevent dyskinesia and fluctuations by drug pharmacokinetics and synergistic effects, and may postpone or reduce the amount of levodopa. Prospective controlled studies are needed to compare the effects of the amantadine-based combination therapy with the standard levodopa therapy for Parkinson\u2019s disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1724003","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T06:33:26Z","timestamp":1774506806000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Amantadine-based combination therapy of Parkinson\u2019s disease to prevent fluctuation and dyskinesia \u2013 experiences from a Parkinson outpatient clinic"],"prefix":"10.3389","volume":"18","author":[{"given":"Christian","family":"Oehlwein","sequence":"first","affiliation":[{"name":"Parkinson's Disease Outpatient Clinic","place":["Gera, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas","family":"Netzel","sequence":"additional","affiliation":[{"name":"Parkinson's Disease Outpatient Clinic","place":["Gera, Germany"]},{"name":"Department of Neuropathology, University of the Saarland","place":["Homburg\/Saar, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Mittmann","sequence":"additional","affiliation":[{"name":"Parkinson's Disease Outpatient Clinic","place":["Gera, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marita","family":"Oehlwein","sequence":"additional","affiliation":[{"name":"Parkinson's Disease Outpatient Clinic","place":["Gera, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter J.","family":"Schulz-Schaeffer","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, University of the Saarland","place":["Homburg\/Saar, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1002\/mds.1090","article-title":"Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature","volume":"16","author":"Ahlskog","year":"2001","journal-title":"Mov Disord"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1212\/01.wnl.0000183359.50822.f2","article-title":"Progression of motor impairment and disability in Parkinson disease: a population-based study","volume":"65","author":"Alves","year":"2005","journal-title":"Neurology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1001\/archneur.1976.00500050019004","article-title":"Six years of high-level levodopa therapy in severely akinetic parkinsonian patients","volume":"33","author":"Barbeau","year":"1976","journal-title":"Arch. 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