| dc.description.abstract | Acetylcholinesterase (AChE) is an important regulatory enzyme that modulates cholinergic synapses by hydrolysis of acetylcholine (ACh), a neurotransmitter involved in many biological processes, especially in memory and cognition. Thus, AChE inhibitors were initially developed for the treatment of cognitive disorders, especially related to Alzheimer's disease. Currently, the inhibitors on the market, such as tacrine, rivastigmine, donepezil, galantamine, although efficient have limitations, such as low bioavailability, gastrointestinal and hepatic side effects. Ebselen, a synthetic organic compound of selenium, is considered a potent pharmacological agent due to its various effects already reported, including antioxidant, anti-inflammatory and neuroprotective effects, and also low toxicity attributed to the molecule. This compound crosses the blood brain barrier and is safe based on cellular toxicity and clinical trials Phase I-III. There is evidence that ebselen inhibits AChE activity ex vivo in brain rats, which generated great interest in further studies about its possible use as a treatment for cognitive dysfunction. In order to increase the knowledge about the mechanisms involved in this action, this study aimed to evaluate the effect of ebselen on the brain AChE activity in vitro by determining its IC50, the kinetic profile via Michaelis-Menten and Lineaweaver-Burk and as reversibility of inhibition by dialysis. The results show that ebselen inhibited AChE activity with an IC50 of 29 μM, similar to the value found for the purified electric eel AChE. Ebselen showed a mixed inhibition due to its increased Km and decreased Vmax. Besides, it was observed a reversible inhibition, because the AChE activity was recovered after 60 min of dialysis. Considering, the results obtained in this study, the use of ebselen as a therapeutic agent for treatment of diseases associated with cholinergic dysfunction should be considered, although behavioral studies of memory are required to support this hypothesis | |
