AMPA RECEPTOR: A REVIEW Review Article POORVASHREE P. JOSHI*, MARYAM MORADIPOUR, AMIT G. NERKAR AND SANJAY D. SAWANT Department of Pharmaceutical and Medicinal Chemistry, STES’s Smt. Kashibai Navale College of Pharmacy, Kondhwa (Bk), Pune, M.S. Email: dragnerkar@gmail.com Received: 13 Mar 2012, Revised and Accepted: 21 April 2012 ABSTRACT α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) are of fundamental importance in the brain. They are responsible for the majority of fast excitatory synaptic transmission, and their overactivation is potently excitotoxic. Recent findings have implicated AMPA receptors in synapse formation and stabilization, and regulation of functional AMPA receptors is the principal mechanism underlying synaptic plasticity. Changes in AMPA receptor activity have been described in the pathology of numerous diseases, such as Alzheimer’s disease, stroke, and epilepsy. Unsurprisingly, the developmental and activity-dependent changes in the functional synaptic expression of these receptors are under tight cellular regulation. The molecular and cellular mechanisms that control the postsynaptic insertion, arrangement, and lifetime of surface-expressed AMPARs are the subject of intense and widespread investigation. For example, there has been an explosion of information about proteins that interact with AMPA receptor subunits, and these interactors are beginning to provide real insight into the molecular and cellular mechanisms underlying the cell biology of AMPA receptors. As a result, there has been considerable progress in this field. The aim of this review is to provide an account of the current state of knowledge about AMPA receptors. Keywords: AMPA receptors, Alzheimer’s disease. INTRODUCTION Receptors are protein molecules, embedded in either the plasma membrane (cell surface receptors) or the cytoplasm (nuclear receptors) of a cell, to which one or more specific kinds of signaling molecules may attach. Molecule which binds (attaches) to a receptor is called a ligand, and may be a peptide (short protein) or other small molecule, such as a neurotransmitter, a hormone, a pharmaceutical drug, or a toxin. Each kind of receptor can bind only certain ligand shapes. Each cell typically has many receptors, of many different kinds. Ligand binding stabilizes a certain receptor conformation (the three-dimensional shape of the receptor protein, with no change in sequence). This is often associated with gain of or loss of protein activity, ordinarily leading to some sort of cellular response. However, some ligands (e.g. antagonists) merely block receptors without inducing any response. Ligand-induced changes in receptors result in cellular changes which constitute the biological activity of the ligands. 1 Amino acid glutamate is the major excitatory neurotransmitter in the mammalian central nervous System (CNS1) and it exerts its physiological effects by binding to a number of different types of glutamate receptors (GluRs). Glutamate receptors can be divided into two functionally distinct categories: those that mediate their effects via coupling to G-protein second messenger systems, the metabotropic glutamate receptors (mGluRs) and ionotropic ligand-gated ion channels. 2 The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptor) is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system (CNS).AMPA receptor is also called as quisqualate receptor. Its name is derived from its ability to be activated by the artificial glutamate analog AMPA. 3 we are here reviewing the importance and medicinal chemistry approach for AMPA receptors as new therapeutic drug target. DISCOVERY The receptor was discovered by Tage Honore and colleagues at the School of Pharmacy in Copenhagen, and published in 1982 in the Journal of Neurochemistry. Fig. 1: It shows the topology of an AMPA receptor subunit International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 4, Issue 3, 2012 A A c c a a d d e e m mi i c c S S c c i i e e n n c c e e s s