Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) (AMPAR)

The Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is a tetrameric ionotropic glutamate receptor that mediates the majority of fast excitatory synaptic transmission in the mammalian central nervous system [2, 11, 14]. Composed of four subunits (GluA1-GluA4), these receptors form cation-selective channels that open upon binding the neurotransmitter glutamate, allowing the influx of sodium and potassium ions to depolarize the postsynaptic membrane [5, 12]. AMPA receptors are fundamental to synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), which serve as the cellular basis for learning and memory [9, 15]. Dysregulation of these receptors is a key factor in the pathophysiology of various neurological disorders, most notably epilepsy, where overactivation leads to neuronal hyperexcitability and seizures [1, 3, 6]. Perampanel is a first-in-class, selective, non-competitive antagonist that targets an allosteric site on the AMPA receptor, effectively reducing excitatory signaling without competing directly with glutamate [1, 8]. This unique mechanism of action provides a potent therapeutic approach for managing focal and generalized seizures while avoiding the direct blockade of the glutamate binding site [4, 6].

Other names

AMPA receptor [2, 11]GluR [11]iGluR [2, 11]Quisqualate receptor [2, 11]Ionotropic glutamate receptor AMPA type [12, 14]

Non-competitive antagonism, competitive antagonism, positive allosteric modulation, and agonism [1, 3, 6, 8, 10, 15].