The effect of the desglycinyl metabolite of remacemide hydrochloride (FPL 12495AA) and dizocilpine (MK-801) on endogenous amino acid release from mouse cortex.

1. In this study the effect of FPL 12495AA, the desglycinyl metabolite of remacemide hydrochloride and dizocilpine (MK-801), on potassium- and veratridine-stimulated release of neurotransmitter amino acids from mouse cortical slices was investigated. 2. Veratridine (20 microM) and potassium (60 mM) produced a preferential release of glutamate and aspartate. Potassium-stimulated release was calcium-dependent, while veratridine-stimulated release was only partially affected by removal of calcium from the medium. 3. FPL 12495AA significantly inhibited veratridine- and potassium-stimulated release of glutamate and aspartate. Lower concentrations of FPL 12495AA were needed to inhibit veratridine-stimulated release of glutamate (12.5 microM) than potassium-stimulated release (100 microM). 4. Dizocilpine significantly inhibited veratridine- and potassium-stimulated release of glutamate and aspartate at concentrations of 100 microM and above. 5. FPL 12495AA and dizocilpine both have an affinity for the ion channel subsite of the N-methyl-D-aspartate (NMDA) receptor. The reduction of potassium-stimulated release of glutamate and aspartate by FPL 12495AA and dizocilpine is probably due to NMDA receptor blockade. 6. FPL 12495AA inhibited veratridine-stimulated release at a concentration of 12.5 microM while dizocilpine was effective only at a concentration of 100 microM. This difference in efficacy is probably due to the higher affinity of FPL 12495AA compared to dizocilpine at the veratridine-binding site on the sodium channel.