With the Jayaraman Lab at UT Health Houston, we show that memantine inhibits calcium-permeable AMPA receptors (CP-AMPARs). This is significant because memantine is an US Food and Drug Administration (FDA) approved drug that selectively inhibits NMDA-subtype ionotropic glutamate receptors (NMDARs) for treatment of dementia and Alzheimer’s.

Regulatory subunits tightly control the function of glutamate receptors, which enables our brains to tune responses to the neurotransmitter glutamate. The structural features of how this occurs were unknown, which is a major barrier in understanding brain function as well as an obstacle to therapeutic development.

Small molecule therapeutics alter the three-dimensional landscape of glutamate receptors to control neurotransmission in disease states. We outline how therapeutic candidates inhibit glutamate receptors, and also observe a new phenomenon called allosteric competition,