Increase of ATP levels by glutamate antagonists is unrelated to neuroprotection.

SUCCINIC dehydrogenase in mouse cortical explant cultures was inhibited by 3-nitropropionic acid (3-NPA). ATP concentrations declined upon application of 3-NPA. At 4 h, ATP levels of cultures treated with 3-NPA alone were no different from those in cultures treated additionally with MK-801 (20 μM), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 μM) or a combination thereof. However, MK-801 and MK-801 plus CNQX mitigated morphological lesions caused by 3-NPA. CNQX alone did not influence the extent of morphological damage. In conclusion, MK-801, at concentrations which were neuro-protective against 3-NPA lesions in cortical explant cultures, did not modify 3-NPA dependent decreases in cellular ATP levels. These data indicate that the neuropro-tective effects of glutamate receptor antagonists in this model are probably receptor mediated and do not involve effects on cellular metabolism.