AMPA 1 Inhibitors

Chemical inhibitors of AMPA 1 can exert their inhibitory effects through various mechanisms directly at the receptor level. NBQX, for example, acts as an antagonist at the AMPA receptor's glutamate-binding site, which is crucial for the receptor's ionotropic function. By binding to this site, NBQX effectively blocks excitatory neurotransmission, preventing the usual flow of ions that would occur upon glutamate binding. Similarly, GYKI 52466 disrupts AMPA receptor function non-competitively by altering the dynamics of the receptor's ion channel, which leads to a decrease in the receptor's activity. Perampanel also specifically targets AMPA receptors, selectively antagonizing them to inhibit the ion flux across the neuronal membrane essential for excitation. IEM-1460 takes a slightly different approach by selectively blocking Ca2+-permeable AMPA receptors, consequently reducing the excitatory synaptic transmission that typically follows ion flow through these channels.

Tezampanel and CFM-2 further contribute to the inhibition of AMPA 1 by binding to the glutamate recognition site and an allosteric modulatory site, respectively. Tezampanel prevents the receptor from activating, while CFM-2's binding leads to inhibition of the receptor's ionotropic activity, effectively silencing the excitatory signals. Topiramate, although more widely recognized for its effects on other receptors, can indirectly influence AMPA receptor-mediated responses through modulation of the receptor subunit composition and, therefore, its ion channel properties. Talampanel and Becampanel both act as competitive antagonists at the glutamate-binding site of AMPA receptors, which inhibits the excitatory neurotransmission mediated by these receptors. ZK200775 similarly inhibits synaptic transmission by restricting the ion channel's opening through its binding to the receptor's glutamate-binding site. Ifenprodil, while primarily targeting NMDA receptors, can also inhibit AMPA receptors associated with certain subunits through allosteric modulation of the receptor activity. Lastly, Selurampanel prevents glutamate from activating AMPA receptors, thereby inhibiting the receptor's ionotropic activity and the resultant excitatory neurotransmission.