ABSTRACT
A number of natural and synthetic molecules including polyamines, protons, Zn2+, steroids, redox reagents, ifenprodil, and ethanol are modulators of NMDA receptors (NMDARs), acting at extracellular sites on the receptors to increase or decrease macroscopic currents and Ca2+ flux through NMDA channels. Some of these modulators, for example Zn2+, polyamines, and protons, are endogenous molecules that may exert important regulatory effects on NMDARs under physiological and/or pathological conditions. Others, for example ifenprodil, are synthetic molecules that serve as experimental tools to study the properties of NMDARs and receptor subtypes and may provide lead compounds for the development of therapeutically useful NMDAR antagonists.
