期刊
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
卷 103, 期 -, 页码 62-70出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejpb.2016.03.017
关键词
Parkinson's disease; Multifunctional dopamine agonist; D-264; Modified cysteine; Blood-brain barrier; Prodrug
资金
- National Institute of Neurological Disorders and Stroke/National Institute of Health [NS047198]
Parkinson's disease (PD) is one of the major debilitating neurodegenerative disorders affecting millions of people worldwide. Progressive loss of dopamine neurons resulting in development of motor dysfunction and other related non-motor symptoms is the hallmark of PD. Previously, we have reported on the neuroprotective property of a potent D3 preferring agonist D-264. In our goal to increase the bioavailability of D-264 in the brain, we have synthesized a modified cysteine based prodrug of D-264 and evaluated its potential in crossing the blood-brain barrier. Herein, we report the synthesis of a novel modified cysteine conjugated prodrug of potent neuroprotective D3 preferring agonist D-264 and systematic evaluation of the hydrolysis pattern of the prodrug to yield D-264 at different time intervals in rat plasma and brain homogenates using HPLC analysis. Furthermore, we have also performed in vivo experiments with the prodrug to evaluate its enhanced brain penetration ability. (C) 2016 Elsevier B.V. All rights reserved.
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