Electrophysiologically potent non-competitive glutamate antagonists at crayfish neuromuscular junctions are also potent inhibitors of [ 3H]MK801 binding to synaptic membranes from rat central nervous system

Abstract

This paper describes effects of non-competitive glutamate antagonists, also known as “glutamate open channel blockers”, at crayfish neuromuscular junctions, on the binding of [ 3H]glutamate, [ 3H]CPP, [ 3H]AMPA, [ 3H]kainate and [ 3H]MK-801 to Triton-treated rat hippocampal synaptic membranes, and [ 3H]MK-801 to Triton-treated synaptic membranes from young rat spinal cord. The compounds tested were oxymatrine, theanine, diltiazem, chlorisondamine, tuberostemonine, trimethaphan, N 2- dansyl- L-arginine -4-t-butylpiperidi amide (TI 233), (1RS,2SR)-5-methyl-1-phenyl-2-(3-piperid-inopropyl amino) hexane-1-ol (MLV-5860) and (4S,5R)-4-(2-methylpropyl)-3-[3-(perhydroazepin-1-yl)propyl]-5-phenyl-1, 3-oxazoline-2-one (MLV-6976). Among compounds tested, MLV-5860, MLV-6976 and TI 233 potently inhibited the binding of [ 3H]MK-801 to Triton-treated rat hippocampal synaptic membranes, but not that of other 3H-labelled ligands. The inhibitory potency of MLV-6976 and MLV-5860 on the binding of [ 3H]MK-801 was similar to that of MK-801. MLV-6976 could also inhibit the inhibitory potency was similar to MK-801. These results suggest that potent glutamate antagonists, acting as open channel blockers at crayfish neuromuscular junction, may have similar pharmacological properties to MK-801 at the mammalian central nervous system, but the reverse may not always be true.