(+)-(S)-trujillon, (+)-(S)-4-(2,2-diphenyl-1,3,2-oxazabolidin-5-oxo)propionic acid, a novel glutamatergic analog, modifies the activity of globus pallidus neurons by selective NMDA receptor activation

Decreased levels of glutamate and changes in several markers of glutamatergic function occur in movement disorders and chronic psychiatric illnesses. Ionotropic glutamate receptors have been implicated in neuronal cell death, and have, therefore, been related to the process of neurodegenerative diseases. Drugs that interact with the glutamatergic system are important tools for the development of better therapies. We examined the effect of a new glutamatergic analog, (+)-(S)-4-(2,2-diphenyl-1,3,2-oxazabolidin-5-oxo)propionic acid, (+)-(S)-Trujillon, on the spontaneous globus pallidus neuronal activity of the anesthetized rat. (+)-(S)-Trujillon excited most pallidal neurons in a dose-dependent manner. Furthermore, blockade of NMDA receptors (NMDARs) inhibited the (+)-(S)-Trujillon-induced excitation, whereas blockade of AMPA/kainate receptors did not. In addition, computational docking studies showed micromolar-range affinities of (+)-(S)-Trujillon for NR2A NMDARs. Our results indicate that (+)-(S)-Trujillon selectively activates NMDARs, an effect that could prove to be a useful tool in the analysis of motor, behavioral, and cognitive disorders, where NMDAR-mediated signaling is altered.