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

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Fatma HaddadRafik Karaman

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, ...Continue Reading

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Citations

Dec 19, 2018·Expert Opinion on Drug Delivery·Anas Najjar, Rafik Karaman
Sep 15, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Serena VittorioLaura De Luca
May 31, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Isra' ZeiadehRafik Karaman
Jul 30, 2020·Molecular Neurobiology·Ajmal AhmadMohammad Moshahid Khan
May 28, 2019·Molecular Biology Reports·Saeid Bagheri-MohammadiMahdi Noureddini
Feb 13, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Adriana TrapaniMassimo Conese
Nov 17, 2020·Frontiers in Cellular and Infection Microbiology·Jing LiuLei Shao
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zeinab Breijyeh, Rafik Karaman
Jan 18, 2019·Bioconjugate Chemistry·Izabela RusieckaPiotr Rekowski
Aug 24, 2021·Journal of Molecular Graphics & Modelling·Mehdi SahihiIsabelle Navizet
May 28, 2021·CNS & Neurological Disorders Drug Targets·Jet Shee TengRhun Yian Koh
May 13, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Kuan-Ju ChenDavid Cipolla

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