Memantine-sulfur containing antioxidant conjugates as potential prodrugs to improve the treatment of Alzheimer's disease.
Eur J Pharm Sci
; 49(2): 187-98, 2013 May 13.
Article
en En
| MEDLINE
| ID: mdl-23454012
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 ß amyloid (Aß) preservation in AD is represented by selective glutamatergic antagonists that possess as well antioxidant capabilities. In the present work, GSH (1) or (R)-α-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 Aß(1-42) aggregation makes at least compound 2 a promising candidate for treatment of AD patients.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Profármacos
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Memantina
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Ácido Tióctico
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Antagonistas de Aminoácidos Excitadores
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Glutatión
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Antioxidantes
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Eur J Pharm Sci
Asunto de la revista:
FARMACIA
/
FARMACOLOGIA
/
QUIMICA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Países Bajos