Inhibition of NMDA receptors and other ion channel types by membrane-associated drugs.
Frontiers in pharmacology January 1, 2025 Elizabeth G Neureiter, M Quincy Erickson-Oberg, Aparna Nigam et al. 4 citations
N-methyl-D-aspartate receptors (NMDARs) are ion channels in brain synapses crucial for learning and memory, but their overactivity contributes to nervous system disorders. Clinically, these disorders are treated with channel-blocking drugs that inhibit NMDARs via two mechanisms: traditional block, where charged drugs enter the channel directly from extracellular fluid after activation, and membrane-to-channel inhibition (MCI), where uncharged drugs first enter the hydrophobic cell membrane, then move into the channel through a fenestration upon receptor activation. MCI is poorly understood despite its clinical relevance. This review examines how membrane-associated drugs inhibit NMDARs and other ion channels, and how the path of drug access may influence therapeutic potential.