Action Of Cholinesterase Inhibitors Research Articles

New arylamidas and arylimidas as potential cholinesterase inhibitors for treatment of Alzheimer’s disease (582.2)

Alzheimer’s disease (AD) is a pathology for which major features are by progressive memory lacking as well as gradual and irreversible disruption of cognitive functions that eventually leads to dementia. Furthermore, Alzheimer’s disease presents a loss of forebrain cholinergic neurons and a progressive decreasing of acetylcholine (ACh). ACh activity in the brain is regulated by the hydrolytic action of cholinesterase (AChE). Therefore, the palliative treatment of Alzheimer's disease is given by the AChE inhibitors.The aim of this work was to evaluate 4 arylamides and 4 arylimides synthesized as potential inhibitors of the AChE according to previous evaluations carried out by means of in silico assays. The selected compounds were synthesized from 4‐chloroaniline or N, N‐dimethyl‐P‐phenyl‐endiamine with maleic anhydride and/or succinic anhydride. The synthesis procedure and chemical characterization is in agreement with proposed structures. The evaluation of these compounds as AChE inhibitors allow us to select two of them which showed notably greater inhibition on the enzyme. Thus, these two compounds could have potential therapeutic in AD.Grant Funding Source: Supported by Consejo Nacional de Ciencia y Tecnología (62488), COFAA and SIP of IPN‐Mexico

2 The underlying mechanism of action of cholinesterase inhibitors and its implications for long-term Alzheimer's disease management

2 The underlying mechanism of action of cholinesterase inhibitors and its implications for long-term Alzheimer's disease management

Inhibition of neurite outgrowth from chick sympathetic neurons by cholinesterase inhibitors is not mediated by binding to cholinesterases

Several studies have suggested a role for cholinesterases in regulating neurite outgrowth. Some acetylcholinesterase (AChE) inhibitors can inhibit neurite outgrowth, but it is unclear if this is due to inhibition of AChE. In this study, the effect of cholinesterase inhibitors on neurite outgrowth from chick sympathetic neurons was examined. Very high (micromolar) concentrations of tacrine and BW284c51 were needed to inhibit neurite outgrowth. In contrast, nanomolar concentrations were required to block cholinesterase activity. No correlation was found between the type of inhibitor or potency of cholinesterase inhibition and inhibition of neurite outgrowth. Both tacrine and BW 284c51 were neurotoxic at concentrations that inhibited outgrowth. Therefore, the action of cholinesterase inhibitors on neurite outgrowth may be due to non-specific toxicity rather than to cholinesterase binding.