AMPAreceptorantagonister

AMPA receptor antagonists are drugs that inhibit the activity of AMPA type glutamate receptors. AMPA receptors, or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, are ionotropic glutamate receptors that mediate fast excitatory synaptic transmission in the central nervous system. By blocking these receptors, AMPA antagonists reduce cation influx, particularly sodium and calcium, thereby dampening neuronal excitability.

The therapeutic potential of AMPA receptor antagonists has been explored in several neurological and psychiatric conditions. In epilepsy, they can lower seizure threshold and have been investigated for status epilepticus control. In stroke and traumatic brain injury studies, they have shown neuroprotective effects by limiting excitotoxic calcium entry. Additionally, in depression and anxiety disorders, some antagonists are being evaluated for their rapid-acting antidepressant-like properties, possibly by modulating glutamatergic tone. In chronic pain management, selective AMPA antagonism may attenuate pain signaling pathways in the spinal cord.

Common examples of AMPA receptor antagonists include perampanel, an FDA‑approved antiepileptic drug, and NBQX and CNQX, which are research compounds used widely in experimental settings. Perampanel binds non‑competitively to an allosteric site on the α1 subunit of the AMPA receptor, providing sustained inhibition. NBQX and CNQX block the amino‑acylation site, thereby competitively inhibiting glutamate binding.

While these agents demonstrate promise, challenges remain regarding tolerance, side effects such as dizziness and cognitive impairment, and the need for selective targeting of receptor subtypes to minimize adverse outcomes. Ongoing clinical trials continue to refine dosing strategies and explore combined therapeutic regimens to harness the benefits of AMPA receptor antagonism in diverse clinical contexts.