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Effects of novel monoamine oxidases and cholinesterases targeting compounds on brain neurotransmitters and behavior in rat model of vascular dementia

AuthorsStasiak, Anna; Mussur, Miroslaw; Unzeta, Mercedes; Samadi, Abdelouahid ; Marco-Contelles, José ; Fogel, W. Agnieszka
KeywordsPermanent bilateral occlusion of the common
Carotid arteries
Vascular dementia
Monoamine oxidases’inhibition
brain biogenic
Issue Date2014
PublisherBentham Science Publishers
CitationCurrent Pharmaceutical Design 20: 161- 171 (2014)
AbstractNeurodegenerative disorders are associated with different neurochemical and morphological alterations in the brain leading to cognitive and behavioural impairments. New therapeutic strategies comprise multifunctional drugs. The aim of the presented studies is to evaluate in vivo the novel compounds - ASS188 and ASS234 - which combine the benzylpiperidine moiety of the acetylcholinesteras (AChE) inhibitor donepezil and the indolyl propargylamino moiety of the monoaminooxidase (MAO) inhibitor, N-[(5-benzyloxy-1-methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine, with respect to their influence on cerebral amine neurotransmitters systems and neuroprotective activity. The presumed therapeutic potential of these compounds has been evaluated following their administration to rats with experimental vascular dementia. A rat model of the permanent bilateral occlusion of the common carotid arteries (BCCAO) and the holeboard memory test were employed for this purpose. Wistar rats were used, either intact or 1 day after BCCAO. ASS188 (1 mg/kg) and ASS234 (5 mg/kg) were given s.c. for 5 consecutive days. Working and reference memory in rats was evaluated by hole-board tests before- and 7 and 12 days after BCCAO. The activities of MAOs, AChE and histamine N-methyltransferase (HMT), as well as cerebral amines concentrations were assayed. A significant inhibition of brain MAO A (>95%) and weaker MAO B (ca 60%) and HMT (<30%) and reduced AChE activities were recorded with a pronounced (2 - 10 fold) increase in the cerebral concentrations of serotonin, dopamine, and noradrenaline and smaller rises (up to 30%) of histamine. The BCCAO rats treated with ASS188 or ASS234 tended to perform holeboard tests better than the BCCAO untreated group, indicating a beneficial effect of the administered therapeutics. © 2014 Bentham Science Publishers.
Identifiersdoi: 10.2174/13816128113199990026
issn: 1381-6128
e-issn: 1873-4286
Appears in Collections:(IQOG) Artículos
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