{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:48:51Z","timestamp":1788241731247,"version":"build-2803163510"},"reference-count":74,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T00:00:00Z","timestamp":1583366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2016R1C1B2006699"],"award-info":[{"award-number":["2016R1C1B2006699"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Tetrabenazine is a US Food and Drug Administration (FDA)-approved drug that exhibits a dopamine depleting effect and is used for the treatment of chorea in Huntington\u2019s disease. Mechanistically, tetrabenazine binds and inhibits vesicular monoamine transporter type 2, which is responsible for importing neurotransmitters from the cytosol to the vesicles in neuronal cells. This transportation contributes to the release of neurotransmitters inside the cell to the synaptic cleft, resulting in dopaminergic signal transmission. The highly potent inhibitory activity of tetrabenazine has led to its advanced applications and in-depth investigation of prodrug design and metabolite drug discovery. In addition, the synthesis of enantiomerically pure tetrabenazine has been pursued. After a series of research studies, tetrabenazine derivatives such as valbenazine and deutetrabenazine have been approved by the US FDA. In addition, radioisotopically labeled tetrabenazine permits the early diagnosis of Parkinson\u2019s disease, which is difficult to treat during the later stages of this disease. These applications were made possible by the synthetic efforts aimed toward the efficient and asymmetric synthesis of tetrabenazine. In this review, various syntheses of tetrabenazine and its derivatives have been summarized.<\/jats:p>","DOI":"10.3390\/molecules25051175","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T09:26:41Z","timestamp":1583486801000},"page":"1175","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Synthesis of Tetrabenazine and Its Derivatives, Pursuing Efficiency and Selectivity"],"prefix":"10.3390","volume":"25","author":[{"given":"Seung-Mann","family":"Paek","sequence":"first","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju Daero 501, Jinju, Gyeongnam 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nrn.2017.130","article-title":"The dopamine motive system: Implications for drug and food addiction","volume":"18","author":"Volkow","year":"2017","journal-title":"Nat. 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