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Xanthine Derivatives as Agents Affecting Non-dopaminergic Neuroprotection in Parkinson’s Disease

[ Vol. 27 , Issue. 12 ]

Author(s):

Alexandra Kasabova-Angelova, Diana Tzankova, Javor Mitkov, Maya Georgieva, Virginia Tzankova, Alexander Zlatkov and Magdalena Kondeva-Burdina*   Pages 2021 - 2036 ( 16 )

Abstract:


Parkinson's Disease (PD) is a neurodegenerative and debilitating disease that affects 1% of the elderly population. Patient’s motor disability results in extreme difficulty to deal with daily activities. Conventional treatment is limited to dopamine replacement therapy, which fails to delay disease’s progression and is often associated with a number of adverse reactions. Recent progress in understanding the mechanisms involved in PD has revealed new molecular targets for therapeutic approaches. Among them, caffeine and xanthine derivatives are promising drug candidates, because of the possible symptomatic benefits in PD. In fact, consumption of coffee correlates with a reduced risk of PD. Over the last decades, a lot of efforts have been made to uncover the therapeutic potential of xanthine structures. The substituted xanthine molecule is used as a scaffold for the synthesis of new compounds with protective effects in neurodegenerative diseases, including PD, asthma, cancer and others. The administration of the xanthines has been proposed as a non-dopaminergic strategy for neuroprotection in PD and the mechanisms of protection have been associated with antagonism of adenosine A2A receptors and Monoamine Oxidase type B (MAO-B) inhibition. The current review summarizes frequently suspected non-dopaminergic neuroprotective mechanisms and the possible beneficial effects of the xanthine derivatives in PD, along with some synthetic approaches to produce perspective xanthine derivatives as non-dopaminergic agents in PD treatment.

Keywords:

Xanthines, caffeine, Parkinson’s disease, neuroprotection, neurodegeneration, non-dopaminergic approach.

Affiliation:

Laboratory of Drug Metabolism and Drug Toxicity, Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, Sofia, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Sofia, Sofia, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Sofia, Sofia, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Sofia, Sofia, Laboratory of Drug Metabolism and Drug Toxicity, Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, Sofia, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Sofia, Sofia, Laboratory of Drug Metabolism and Drug Toxicity, Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, Sofia



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