ELECTROPHYSIOLOGICALLY POTENT NONCOMPETITIVE GLUTAMATE ANTAGONISTS AT CRAYFISH NEUROMUSCULAR-JUNCTIONS ARE ALSO POTENT INHIBITORS OF [H-3] MK801 BINDING TO SYNAPTIC-MEMBRANES FROM RAT CENTRAL-NERVOUS-SYSTEM

This paper describes effects of non-competitive glutamate antagonists, also known as ''glutamate open channel blockers'', at crayfish neuromuscular junctions, on the binding of [H-3]glutamate, [H-3]CPP, [H-3]AMPA, [H-3]kainate and [H-3]MK-801 to Triton-treated rat hippocampal synaptic membranes, and [H-3]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-butylpiperidine 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 [H-3]MK-801 to Triton-treated rat hippocampal synaptic membranes, but not that of other H-3-labelled ligands. The inhibitory potency of MLV-6976 and MLV-5860 on the binding of [H-3]MK-801 was similar to that of MK-801. MLV-6976 could also inhibit the binding of [H-3]MK-801 to Triton-treated synaptic membranes from young rat spinal cords, and 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.