NBQX is a Highly Selective and Competitive AMPA Receptor Antagonist

Glutamate is a predominant neurotransmitter released from excitatory neurons related to the fast synaptic excitation. The released glutamates diffuse across the synaptic cleft and generate fast EPSPs through binding to ionotropic glutamate receptors. AMPA receptors regulate the fast synaptic excitation in brain regions that are related to epilepsy. Specifically, AMPA receptor antagonists markedly reduce epileptiform. It also inhibit the spread of epileptic discharges in both animal seizure models and human epilepsy. In addition, growing evidence validate the critical role of AMPA receptors in epileptic seizures, and suggest that AMPA receptors may be a potential target for epilepsy therapy.

NBQX is a competitive AMPA receptor antagonist and has a property that suppressed focal electrographic seizures in epileptic mice . Recently, it showed that NBQX blocks the development of spontaneous recurrent seizures when treatment after neonatal seizures. Consistently, noncompetitive AMPA antagonist perampanel improved the performance of partial seizures, suggesting a remarkable antiepileptogenic effect.

Perineuronal nets (PNNs) serve as condensed ECM structures, which surround parvalbumin-positive inhibitory interneurons and play a critical role in neuronal cell development. CSPGs are crucial components of PNNs, which have been suggested to be a critical factor regulating synaptic plasticity. Aberrant PNN signaling could induce the dysfunctions of central nervous system such as epilepsy, stroke, Alzheimer’s disease, schizophrenia and addiction. The plant lectins Wisteria floribunda agglutinin (WFA) could visualize PNNs by binding to N-acetylgalactosamine residue. Therefore, we use WFA-labeled neurons to evaluate the numbers of PNNs in the current investigation. The three major ECM components of PNNs are tenascin-R, aggrecan and neurocan. Specially, they serve as important contributors to formation and stabilization of PNNs functions.

NBQX serves as a highly selective and competitive AMPA receptor antagonist.

Also, the inhibitor shows a high affinity for AMPA and kainate binding sites with little or no affinity for the glutamate recognition site on the NMDA receptor complex.

Moreover, NBQX (FG9202; 20 mg/kg, i.p.; for 3 days) decreases seizures induced by PTZ. It exhibits Neuroprotectivet aivity in a focal ischaemia model in the rat when given as an i.v. bolus dose of 30 mg/kg at the time of MCA occlusion and again at 1 h post occlusion.

Wen Chen, et al. AMPA Receptor Antagonist NBQX Decreased Seizures by Normalization of Perineuronal Nets. PLoS One. 2016 Nov 23;11(11):e0166672.