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NMDA is the excitatory amino acid receptor subtype that is most thoroughly studied. It is an ionotropic receptor with Mg2+ blockage in a voltage-dependent manner. Functional NMDA receptor consists of a heterodimer of NMDAR1 and NMDAR2 subunits. Alternative splicing of the products of exons 5, 21 and 22 results in 7 naturally occuring isoforms. lmpotant allosteric binding sites on the NMDA receptors are Zn2+, glycine and polyamine binding sites. Since the competitive NMDA antagonists and the noncompetitive antagonists are mostly associated with psychotomimetic effects, attention has recently been paid toward the development of ligands that bind to the glycine and polyamine binding sites. The most promising compounds that have potentials as anticonvulsants are partial and competitive antagonists of the glycine binding site and competitive antagonists of the polyamine bindings sites.
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