TACRINE HYBRIDS - NMDAR antagonist
Hybrid molecules represent a new and different strategy in the treatment of AD. We suppose that these compounds are able to hit additional targets relevant to AD and thus succeed in overcoming the multifactorial pathogenesis of this disease. These compounds may be beneficial since they would be expected to lessen the hazard of drug-drug interactions and simplify their pharmacodynamic and pharmacokinetic studies.
AlzheimerΓÇÖs disease (AD) is the most common cause of dementia in people aged 60 years and older, and accounts for approximately 75% of the total dementia cases worldwide. The continuous research in this field has contributed to delineate AD as a multifactorial syndrome with several biological targets involved in its etiology. Thus the curative paradigm of one-compound one-target that has been followed so far has not reached the desired expectations. The research focus moved towards single hybrid molecule targeting two or more mechanisms involved in disease pathophysiology.
A combination of the AChE inhibitor and N-methyl-D-aspartate receptor (NMDAR) antagonist (memantine) is now a standard treatment of AD. Therefore there were synthetized hybrid molecules affecting both targets ΓÇô cholinesterases and NMDAR. Our hybrids are able to inhibit acetylcholinesterase and butyrylcholinesterase and furthermore inhibit excessive calcium influx induced by chronic overstimulation of the NMDAR in AD patients.
美国
