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Multifunctional neuroprotective derivatives of rasagiline as anti-alzheimer’s disease drugs

Content Provider	Springer Nature Link
Author	Weinreb, Orly Mandel, Silvia Bar Am, Orit Yogev Falach, Merav Avramovich Tirosh, Yael Amit, Tamar Youdim, Moussa B. H.
Copyright Year	2009
Abstract	The recent therapeutic approach in which drug candidates are designed to possess diverse pharmacological properties and act on multiple targets has stimulated the development of the multimodal drugs, ladostigil (TV3326) [(N-propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate] and the newly designed multifunctional antioxidant iron chelator, M-30 (5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline). Ladostigil combines, in a single molecule, the neuro-protective/neurorestorative effects of the novel anti-Parkinsonian drug and selective monoamine oxidase (MAO)-B inhibitor, rasagiline (Azilect, Teva Pharmaceutical Co.) with the cholinesterase (ChE) inhibitory activity of rivastigmine. A second derivative of rasagiline, M-30 was developed by amalgamating the propargyl moiety of rasagiline into the skeleton of our novel brain permeable neuroprotective iron chelator, VK-28. Preclinical experiments showed that both compounds have anti-Alzheimer’s disease activities and thus, the clinical development is oriented toward treatment of this type of dementia. This review discusses the multimodal effects of two rasagiline-containing hybrid molecules, namely ladostigil and M-30, concerning their neuroprotective molecular mechanisms in vivo and in vitro, including regulation of amyloid precursor protein processing, activation of protein kinase C, and mitogen-activated protein kinase signaling pathways, inhibition of cell death markers and upregulation of neurotrophic factors. Altogether, these scientific findings make these multifunctional compounds potentially valuable drugs for the treatment of Alzheimer’s disease.
Starting Page	163
Ending Page	174
Page Count	12
File Format	PDF
ISSN	19337213
Journal	NeuroRX
Volume Number	6
Issue Number	1
e-ISSN	18787479
Language	English
Publisher	Springer-Verlag
Publisher Date	2009-01-01
Publisher Institution	American Society for Experimental NeuroTherapeutics
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Alzheimer’s disease amyloid precursor protein multifunctional drugs propargyl moiety cholinesterase inhibitor iron chelator Neurosciences Neurology Neurosurgery Neurobiology
Content Type	Text
Resource Type	Article
Subject	Neurology (clinical) Pharmacology Pharmacology (medical)

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