In particular, the potential energy distribution analysis was performed to assign IR signals. In addition, IR spectra were calculated and compared with the experimental data. The compounds were also characterized by infrared spectroscopy. This paper reports the thermal stability and thermal degradation of six derivatives of indole by means of TG-DSC (in air) and TG-FTIR (in nitrogen) techniques. 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. More interest was focused on metabotropic receptors, which are GPSR’s and can be modulated both by orthosteric and allosteric modulators. Their usefulness as drugs was rather low, due to the involvement in the excitatory tract.
In the meantime numerous orthosteric ligands, both agonists and antagonists were developed especially for NMDA ion channels. Since then, many subtypes of ionotropic and metabotropic glutamate receptors were recognized, together with their localization and functions. In 1994 ligand binding site was recognized at the junction of two subunits S1-S2 in the ligand-binding domain. Recognition of the sequence and first cloning were done at the beginning of 90’. Presence of at least three classes of ionotropic receptors was confirmed at the beginning of 80’. Receptors of glutamic acid are known for over 30 years for their action and for about 20 years for their structure. In particular, the aspects of iGluR structure which are important for drug design, like the molecular characterstics of the ligand binding sites, are depicted in detail. This review summarizes experimental and computational efforts to determine iGluR molecular architecture and focus on the above listed achievements of the last years. The data about general topology and modular composition of iGluRs as well as numerous crystal structures of ligand binding domains of many iGluR subtypes has been supplemented with the first molecular models of the whole receptor protein, followed by the first crystal structures of N-terminal domains and finally by the first crystal structure of the whole tetrameric iGluR. Recently, tremendous progress has been made in structure elucidation and understanding of the functioning of iGluRs. Knowledge about the structure of ionotropic glutamate receptors (iGluRs) at atomic resolution is vital for the determination of their physiological and pathological importance and, thus, for drug design. Although just a few glutamate receptor ligands have turned out to be clinically useful, primarily because of unfavorable psychotropic side effects, the glutamate system remains an attractive molecular target in the treatment of epilepsy, neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's chorea), schizophrenia, ischemia, pain, alcoholism and mood disorders.
L-glutamate is the major excitatory neurotransmitter in the central nervous system (CNS).