Research

Butyrylcholinesterase inhibitors for alleviating symptoms of Alzheimer's disease

Code:

Z1-9195

Range:

01. July 2018 - 30. June 2020

Range:

0,5 FTE

Leader:

Urban Košak

Field:

1-09 Natural sciences and Mathematics - Pharmacy

Abstract:

Memory and cognitive deficits of patients with AD are the result of severely decreased brain levels of ACh. Currently approved ChEs inhibitors in AD therapy (donepezil, galantamine and rivastigmine) alleviate symptoms of the disease by increasing brain levels of ACh. They achieve this by preventing the breakdown of ACh through inhibition of the enzymes that hydrolyze it. These enzymes are called ChEs and two types are known: AChE and BChE. Donepezil, galantamine, rivastigmine and other AChE inhibitors however, have a major drawback. They inhibit AChE not only in the brain but also in the PNS and ANS. It is the inhibition of AChE in the PNS and ANS which is the cause of adverse cholinergic effects (nausea, diarrhea, vomiting, and tremors) of these drugs. This limits both their dosing and clinical efficacy in advanced stages of AD. The shortcoming of currently approved ChEs for alleviating symptoms of AD can be overcome using selective BChE inhibitors which raise brain levels of ACh and improve memory and cognitive performance of mice without any cholinergic adverse effects.