Место издания:XX Mенделеевский съезд по общей и прикладной химии Ekaterinburg Ekaterinburg
Первая страница:421
Аннотация:Glutamatergic system plays an important role in mammals CNS functioning. Positive
allosteric modulators (PAMs) of AMPA receptors (one of types of ionotropic glutamate
receptors) have a significant influence on learning and memory consolidation. It is also
shown in experiments that the intensive ion currents caused by such modulators and
further postsynaptic membrane depolarization launch the mechanism of gene expression
responsible for the synthesis of NGF (nerve growth factor) and BDNF (brain-derived
neurotrophic factor). Thus the drugs having this mechanism of action could be efficient
for the treatment of neurodegenerative diseases. The negative allosteric modulators of
another important type of ionotropic glutamate receptors, NMDA receptors, could serve as
neuroprotectors restricting the excessive calcium influx into neurons.
In this report the techniques are considered for computer-aided design of AMPA and
NMDA receptor modulators based on new scaffolds as well as approaches to their synthesis
and the results of physiological activity studies. New modulators were found with a unique
combination of properties including picomolar activity and low toxicity.