The effects of N‐methyl‐d‐aspartate (NMDA) on the free intracellular Ca²⁺ concentration ([Ca²⁺]_i) and the energy state in superfused cerebral cortical slices have teen studied using ¹⁹F‐ and ³¹P‐nuclear magnetic resonance spectroscopy. [Ca²⁺]_i was measured using the calcium indicator 1,2‐bis(2‐amino‐5‐fluorophenoxy)ethane‐N.N.N′.N′‐tetraacetic acid (5FBAPTA). NMDA (10 μM) in the absence of extracellular Mg²⁺ caused the expected rise in [Ca²⁺]_i but produced an impairment of the energy state: the phosphocreatine (PCr) content was decreased by 42%, and the P_i/PCr ratio was increased by 55%. There was no detectable change in ATP or free intracellular Mg²⁺ concentration. Increasing the NMDA concentration in the superfusing medium to 100 or 400 μM caused no further increase in [Ca²⁺]_i or further decrease in PCr content, but the P_i/PCr ratio continued to rise. The impairment of the energy state preceded the effect on [Ca²⁺]_i, and these changes were irreversible on return to control conditions. Repeating the experiments in the presence of 1.2 mM extracellular Mg²⁺ resulted in similar changes in the energy state, with no change in [Ca²⁺]_i. The possibilities that the effects were due to membrane depolarisation or to the presence of 5FBAPTA within the tissues were eliminated. The results suggest that low concentrations (10 μM) of NMDA produce an impaired energy state independent of the presence of extracellular Mg²⁺ and that the decreased energy state is not due to the changes in [Ca²⁺]_i, which are seen only in the absence of extracellular Mg²⁺.

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