CHARACTERIZATION OF D-3,4-CYCLOPROPYLGLUTAMATES AS N-METHYL-D-ASPARTATE RECEPTOR AGONISTS

The 4 configurational isomers of d-3,4-cyclopropylglutamate (d-CGA) have been synthesized and analyzed for their interactions as excitatory amino acid recognition sites. Additionally, functional assessment of the action of these compounds at the N-methyl-d-aspartate (NMDA) receptor was performed. All 4 analogs function as agonists at the NMDA receptor as evidenced by their ability to stimulate [3H]MK-801 binding to the coupled PCP recognition site. Furthermore, the rank order of potency of these compounds in stimulating [3H]MK-801 binding corresponds with their Ki values for the displacement of NMDA-selective l-[3H]glumate and [3H]CGS-19755 binding (d-CGA-C>d-CGA-B>d-CGA-D>d-CGA-A). The d-CGA-C isomer has affinity and potency at the NMDA receptor similar to the endogenous agonist, l-glutamate. This high potency coupled with greater specificity than l-glutamate, makes d-CGA-C a potentially useful pharmacological tool for the study of this receptor. © 1990.