期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 49, 期 2, 页码 187-198出版社
ELSEVIER
DOI: 10.1016/j.ejps.2013.02.013
关键词
Alzheimer's disease; Memantine conjugates; A beta(1-42) aggregation; BBB permeation
资金
- Ministero dell' Istruzione, dell'Universita e della Ricerca (MIUR)
The approved treatments for Alzheimer's disease (AD) exploit mainly a symptomatic approach based on the use of cholinesterase inhibitors or N-methyl-D-aspartate (NMDA) receptor antagonists. Natural antioxidant compounds, able to pass through the blood-brain barrier (BBB), have been extensively studied as useful neuroprotective agents. A novel approach towards excitotoxicity protection and oxidative stress associated with excess beta amyloid (A beta) preservation in AD is represented by selective glutamatergic antagonists that possess as well antioxidant capabilities. In the present work, GSH (I) or (R)-alpha-lipoic acid (LA) (2) have been covalently linked with the NMDA receptor antagonists memantine (MEM). The new conjugates, proposed as potential antialzheimer drugs, should act both as glutamate receptor antagonists and radical scavenging agents. The physico-chemical properties and in vitro membrane permeability, the enzymatic and chemical stability, the demonstrated in vitro antioxidant activity associated to the capacity to inhibit A beta(1-42) aggregation makes at least compound 2 a promising candidate for treatment of AD patients. (C) 2013 Elsevier B.V. All rights reserved.
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