AMPA receptor antagonists 

AMPA receptor antagonists are anticonvulsants used in patients with epilepsy in the treatment of partial-onset seizures. They are non-competitive antagonists of AMPA receptors, a type of glutamate receptor that participates in excitatory neurotransmission.

A number of AMPA receptor antagonists have been employed in clinical trials (eg, talampanel), but only one has been approved for clinical use, This drug, perampanel (Fycompa), is capable of maintaining the closure of AMPA receptors even in the presence of elevated glutamate levels.

Gabexate and camostat were found to be inactive. Other compounds preferentially inhibited calcium-permeable AMPA receptors with IC₅₀ values of 30-60 µM. DAPI and furamidine were also active against CI-AMPARs with IC₅₀s of 50-60 μM, while others showed poor activity.

AMPA receptor agonists such as glutamate and AMPA induce contraction of the ligand binding core so that domain 1 and domain 2 close by ∼20°, resulting in channel gating (Fig. 2). Like other competitive antagonists, NS1209 occupies the ligand binding site and hinders closure of the two domains.