Dopamine and Levodopa Prodrugs for the Treatment of Parkinson’s Disease

dc.contributor.author Haddad, Fatma
dc.contributor.author Sawalha, Maryam
dc.contributor.author Khawaja, Yahya
dc.contributor.author Najjar, Anas
dc.contributor.author Karaman, Rafik
dc.date.accessioned 2019-12-11T12:40:54Z
dc.date.available 2019-12-11T12:40:54Z
dc.date.issued 2017-12-25
dc.description.abstract Background: Parkinson’s disease is an aggressive and progressive neurodegenerative disorder that depletes dopamine (DA) in the central nervous system. Dopamine replacement therapy, mainly through actual dopamine and its original prodrug L-dopa (LD), faces many challenges such as poor blood brain barrier penetration and decreased response to therapy with time. Methods: The prodrugs described herein are ester, amide, dimeric amide, carrier-mediated, peptide transport-mediated, cyclic, chemical delivery systems and enzyme-models prodrugs designed and made by chemical means, and their bioavailability was studied in animals. Results: A promising ester prodrug for intranasal delivery has been developed. LD methyl ester is currently in Phase III clinical trials. A series of amide prodrugs were synthesized with better stability than ester prodrugs. Both amide and dimeric amide prodrugs offer enhanced blood brain barrier (BBB) penetration and better pharmacokinetics. Attaching LD to sugars has been used to exploit glucose transport mechanisms into the brain. Conclusions: Till now, no DA prodrug has reached the pharmaceutical market, nevertheless, the future of utilizing prodrugs for the treatment of PD seems to be bright. For instance, LD ester prodrugs have demonstrated an adequate intranasal delivery of LD, thus enabling the absorption of therapeutic agents to the brain. Most of the amide, cyclic, peptidyl or chemical delivery systems of DA prodrugs demonstrated enhanced pharmacokinetic properties. en_US
dc.identifier.issn 1420-3049
dc.identifier.uri https://dspace.alquds.edu/handle/20.500.12213/5019
dc.language.iso en en_US
dc.publisher MDPI en_US
dc.subject dopamine en_US
dc.subject levodopa en_US
dc.subject prodrug en_US
dc.subject Parkinson’s disease en_US
dc.subject blood brain barrier en_US
dc.title Dopamine and Levodopa Prodrugs for the Treatment of Parkinson’s Disease en_US
dc.type Article en_US
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