Abstract

AIM To investigate age related alterations in glutamate N-methyl-D-aspartate (NMDA) receptor binding produced by the modulatory compounds glutamate, glycine, and magnesium (Mg²⁺) sulphate.

METHODS The effects produced by glutamate plus glycine, and Mg²⁺ on the binding of [³H]MK-801, a ligand for theN-methyl-D-aspartate ion channel phencyclidine site, were measured in membrane preparations made from prefrontal cortex from human neonate (n = 5), infant (n = 6), and adult (n = 6) necropsy brains.

RESULTS Neonatal brains had the least [³H]MK-801 binding, suggesting either a low density of NMDA receptors or a more restricted access of [³H]MK-801 to cation channel sites. Infant brains had the most [³H]MK-801 binding which was stimulated to a greater extent by L-glutamate (100 μM) and glycine (10 μM) than in neonatal and adult brains. Mg²⁺ invariably inhibited [³H]MK-801 binding. However, the Mg²⁺IC₅₀ value was higher in neonatal brain (3.6 mM) than infant (1.4 mM) and adult (0.87 mM) brains.

CONCLUSION Infant brain may have excess NMDA receptors which are hyper responsive to glutamate and glycine. The lower potency of Mg²⁺ to inhibit [³H]MK-801 binding in neonatal cortex may be because newborn babies have NMDA receptors without the normal complement of Mg²⁺ sites. The findings suggest that therapeutic NMDA receptor block in neonates requires higher concentrations of magnesium sulphate in brain tissue.