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KDS2010, a Newly Developed Reversible MAO-B Inhibitor, as an Effective Therapeutic Candidate for Parkinson’s Disease
- Source :
- Neurotherapeutics
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Monoamine oxidase-B (MAO-B) is a well-established therapeutic target for Parkinson’s disease (PD); however, previous clinical studies on currently available irreversible MAO-B inhibitors have yielded disappointing neuroprotective effects. Here, we tested the therapeutic potential of KDS2010, a recently synthesized potent, selective, and reversible MAO-B inhibitor in multiple animal models of PD. We designed and synthesized a series of α-aminoamide derivatives and found that derivative KDS2010 exhibited the highest potency, specificity, reversibility, and bioavailability (> 100%). In addition, KDS2010 demonstrated significant neuroprotective and anti-neuroinflammatory efficacy against nigrostriatal pathway destruction in the mouse MPTP model of parkinsonism. Treatment with KDS2010 also alleviated parkinsonian motor dysfunction in 6-hydroxydopamine-induced and A53T mutant α-synuclein overexpression rat models of PD. Moreover, KDS2010 showed virtually no toxicity or side effects in non-human primates. KDS2010 could be a next-generation therapeutic candidate for PD. Supplementary Information The online version contains supplementary material available at 10.1007/s13311-021-01097-4.
- Subjects :
- Male
Monoamine Oxidase Inhibitors
Parkinson's disease
α-Aminoamide derivative
Monoamine oxidase
Nigrostriatal pathway
Pharmacology
Neuroprotection
Mice
chemistry.chemical_compound
Drug Development
Parkinsonian Disorders
medicine
Animals
Pharmacology (medical)
MAO-B inhibitor
Monoamine Oxidase
Reactive glia
Dose-Response Relationship, Drug
business.industry
MPTP
Parkinsonism
medicine.disease
Rats
Macaca fascicularis
Treatment Outcome
medicine.anatomical_structure
chemistry
Toxicity
Parkinson’s disease
Original Article
Female
Neurology (clinical)
Monoamine oxidase B
business
Subjects
Details
- ISSN :
- 18787479 and 19337213
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Neurotherapeutics
- Accession number :
- edsair.doi.dedup.....08c8d5238ee55e8f326fa5df429e9ef7