ST09, a Novel Thioester Derivative of Tacrine, Alleviates Cognitive Deficits and Enhances Glucose Metabolism in Vascular Dementia Rats.
CNS Neurosci Ther
; 22(3): 220-9, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-26813743
ABSTRACT
AIMS:
Chemical entities containing mercapto group have been increasingly attractive in the therapy of central nerve system (CNS) diseases. In the recent study, we screened a series of mercapto-tacrine derivatives with synergistic neuropharmacological profiles in vitro.METHODS:
We investigated the effect and mechanism of ST09, a thioester derivative of tacrine containing a potential mercapto group, on the vascular dementia (VaD) model of rat induced by bilateral common carotid arteries occlusion (2-VO).RESULTS:
ST09 and its active metabolite ST10 retained excellent inhibition on acetylcholinesterase (AChE) activity. ST09 significantly attenuated the 2-VO-induced impairment in spatial acquisition performance and inhibited the 2-VO-induced rise of AChE activity. In the VaD model, ST09 attenuated the oxidative stress and decreased the apoptosis in the cortex and hippocampus. Compared with donepezil, ST09 exhibited a better effect on the regeneration of free thiols in 2-VO rats. Interestingly, ST09, not donepezil, greatly improved glucose metabolism in various brain regions of 2-VO rats using functional imaging of (18) F-labeled fluoro-deoxyglucose (FDG) positron emission tomography (PET).CONCLUSIONS:
ST09 may serve as a more promising agent for the therapy of VaD than tacrine owing to the introduction of a potential mercapto group into the parent skeleton.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Demência Vascular
/
Niacinamida
/
Transtornos Cognitivos
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Nootrópicos
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Glucose
Limite:
Animals
Idioma:
En
Revista:
CNS Neurosci Ther
Assunto da revista:
NEUROLOGIA
/
TERAPEUTICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China