Properties of AMPA type glutamate receptors widely presented within mammalian central nervous system are reviewed. AMPA receptors belong to ionotropic subclass of glutamate receptors and participate in fast excitatory glutamatergic transmission in the brain. Molecular structure of AMPA receptors consists of several subunits (GluRA1-GluRA4), which display various sensitivity to receptor ligands. These receptors are named according to their selective agonist α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). АМРА receptor modulators represented by several chemical groups: pyrrolidinones (aniracetam), benzothiodiazinedioxides, benzylpiperidines and biarylpropylsulphonamides. These compounds facilitate AMPA receptor-mediated glutamatergicneurotransmission. AMPA receptor modulators enhance cognitive functions (learning and memory), reveal anxiolytic and antidepressant action, suppress the effects of psychostimulant agents, potentiate the effects of antipsychotic drugs, display neuroprotective properties. Positive modulation of AMPA receptor-associated ionic channels was shown to underline the mode of action of these substances that results in enhancement of long-term potentiation (LTP) and increasing neurotrophic factors expression. Preliminary clinical results have shown positive therapeutic effect of these substances in patients with cognitive impairment.
Arai A., Kessler M., Rogers G., Lynch G. (1996) J. Pharmacol. Exp. Ther, 278(2), 627- 638. Scholar google search
Shepherd T.A., Aikins J.A., Bleakman D., Cantrell B.E., Reahck J.R., Simon R.L., Smith E.C.R., Stephenson G.A., Zimmerman D.M., Mandelzys A., Jarvie K.R., Ho K., Deverill M., Kamboj R.K. (2002) J. Med. Chem., 45, 2101- 2111. Scholar google search
Miu P., Jarvie K., Radhakrishnan V., Gates M., Ogden A., Ornstein P., Zarrinmayeh H., Ho K., Peters D., Grabell J., Gupta A., Zimmerman D., Bleakman D. (2001) Neuropharmacology, 40(8), 976- 983. Scholar google search
Murray Т.К., Whalley K., Robinson C., Ward M.A., Hicks C.A., Lodge D., Vandergriff J., Baumbarger P., Suida E., Gates M., Ogden A.M., Skolnick P., Zimmerman D.M., Nisenbaum E.S., Bleakman D., O'Neill M.J. (2003) J. Pharmacol. Exp. Ther., 306(2), 752- 762. Scholar google search