Title:Potential Future of New Glutamate Agonists and Antagonists Development
VOLUME: 18 ISSUE: 4
Author(s):Dariusz Matosiuk*
Affiliation:Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Faculty of Pharmacy, Medical University, Chodzki 4A, 20-093 Lublin
Keywords:iGluR, mGluR, NMDA, AMPA, KA, AMPA auxiliary proteins, allosteric mGluR PAM and NAM modulators.
Abstract:Receptors of glutamic acid are known for over 30 years for their action and for about 20 years for
their structure. Presence of at least three classes of ionotropic receptors was confirmed at the beginning of 80’.
Recognition of the sequence and first cloning were done at the beginning of 90’. In 1994 ligand binding site was
recognized at the junction of two subunits S1-S2 in the ligand-binding domain.
Since then, many subtypes of ionotropic and metabotropic glutamate receptors were recognized, together with
their localization and functions.
In the meantime numerous orthosteric ligands, both agonists and antagonists were developed especially for
NMDA ion channels. Their usefulness as drugs was rather low, due to the involvement in the excitatory tract.
More interest was focused on metabotropic receptors, which are GPSR’s and can be modulated both by orthosteric
and allosteric modulators.
It seems like allosterism could be considered as promising future for glutamate receptors and ion channels,
especially when first allosteric negative modulators of the mGluR2 went close into the clinical trial.
