Molecular analysis of the blocking mechanisms of AMPAergic glutamate receptors: Development of a new therapeutic strategy for neurodegenerative diseases

By means of modern electrophysiological processes, in particular the,patch clamp" technique in combination with a process for the ultrarapid change of solvent at a membrane patch, which makes the experimental investigation of rapid, post-synaptic processes possible, the in vitro pharamcological mechanisms of recombinant AMPA-type glutamate receptors were examined at the molecular level. With these experiments we were able to detect the blocking mechanisms of various classes of compounds such as pyrazines and adamantanes at the various recombinant AMPA-type glutamate receptors on individual channel proteins. We found that pyrazine derivatives exert a purely competitive blockage at the receptors while adamantanes effect a combined open channel blockade and a competitive blockage at the receprtors. With the exact knowledge and analysis of the molecular mechanisms of receptor blocking it should be possible to develop new, effective therapeutic strategies against processes of acute or chronic neurodegeneration.