{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T22:30:19Z","timestamp":1779143419903,"version":"3.51.4"},"reference-count":90,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2008,1,16]],"date-time":"2008-01-16T00:00:00Z","timestamp":1200441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Parkinson`s disease (PD) is a progressive, neurodegenerative disorder whichinvolves the loss of dopaminergic neurons of the substantia nigra pars compacta. Currenttherapy is essentially symptomatic, and L-Dopa (LD), the direct precursor of dopamine(DA), is the treatment of choice in more advanced stages of the disease. Substitutiontherapy with LD is, however, associated with a number of acute problems. The peripheralconversion of LD by amino acid decarboxylase (AADC) to DA is responsible for thetypical gastrointestinal (nausea, emesis) and cardiovascular (arrhythmia, hypotension) sideeffects. To minimize the conversion to DA outside the central nervous system (CNS) LD isusually given in combination with peripheral inhibitors of AADC (carbidopa andbenserazide). In spite of that, other central nervous side effects such as dyskinesia, on-offphenomenon and end-of-dose deterioration still remain. The main factors responsible forthe poor bioavailability and the wide range of inter- and intra-patient variations of plasmalevels are the drug\u2019s physical-chemical properties: low water and lipid solubility, resultingin unfavourable partition, and the high susceptibility to chemical and enzymaticdegradation. In order to improve the bioavailability, the prodrug approach appeared to bethe most promising and some LD prodrugs have been prepared in an effort to solve theseproblems. We report here a review of progress in antiparkinson prodrugs, focusing onchemical structures mainly related to LD, DA and dopaminergic agonists.<\/jats:p>","DOI":"10.3390\/molecules13010046","type":"journal-article","created":{"date-parts":[[2008,10,2]],"date-time":"2008-10-02T12:45:09Z","timestamp":1222951509000},"page":"46-68","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Antiparkinson Prodrugs"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3042-2234","authenticated-orcid":false,"given":"Antonio","family":"Di Stefano","sequence":"first","affiliation":[{"name":"Department of Drug Sciences, \u201cG. d'Annunzio\u201d University, School of Pharmacy, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piera","family":"Sozio","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, \u201cG. d'Annunzio\u201d University, School of Pharmacy, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura Serafina","family":"Cerasa","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, \u201cG. d'Annunzio\u201d University, School of Pharmacy, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2008,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nrn1868","article-title":"Expanding insights of mitochondrial dysfunction in Parkinson\u2019s disease","volume":"7","author":"Muqit","year":"2006","journal-title":"Nat. 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