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The effect of the desglycinyl metabolite of remacemide hydrochloride (FPL 12495AA) and dizocilpine (MK‐801) on endogenous amino acid release from mouse cortex
Author(s) -
Srinivasan Jayashri,
Richens Alan,
Davies John A.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb15109.x
Subject(s) - veratridine , dizocilpine , chemistry , nmda receptor , glutamate receptor , potassium , calcium , pharmacology , sodium , biochemistry , receptor , sodium channel , biology , organic chemistry
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 μ m ) 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 μ m ) than potassium‐stimulated release (100 μ m ). 4 Dizocilpine significantly inhibited veratridine‐ and potassium‐stimulated release of glutamate and aspartate at concentrations of 100 μ m 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 μ m while dizocilpine was effective only at a concentration of 100 μ m . 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.