(+)-(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

Authors

  • Juan M. Araujo-Alvarez,

    1. Department of Physiology and Pharmacology, National Polytechnic Institute School of Medicine, México D.F., México
    Search for more papers by this author
  • José G. Trujillo-Ferrara,

    1. Department of Physiology and Pharmacology, National Polytechnic Institute School of Medicine, México D.F., México
    Search for more papers by this author
  • Daniel Ponce-Franco,

    1. Department of Physiology and Pharmacology, National Polytechnic Institute School of Medicine, México D.F., México
    Search for more papers by this author
  • Jose Correa-Basurto,

    1. Department of Physiology and Pharmacology, National Polytechnic Institute School of Medicine, México D.F., México
    Search for more papers by this author
  • Alfonso Delgado,

    1. Department of Physiology and Neuroscience, Autonomous University of Chihuahua School of Medicine, Chihuahua Chih, México
    Search for more papers by this author
  • Enrique Querejeta

    Corresponding author
    1. Department of Physiology and Pharmacology, National Polytechnic Institute School of Medicine, México D.F., México
    • Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del IPN. Plan de San Luis y Díaz Mirón Col. Casco de Santo Tomás, C.P. 11340, México D.F., México

    Search for more papers by this author

Abstract

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. 23:429–437, 2011. © 2008 Wiley-Liss, Inc.

Ancillary