Specificity and potency of N-methyl-D-aspartate glycine site antagonists and of mephenesin on the rat spinal cord in vitro.
The potency, specificity and reversibility of various presumed glycine site N-methyl-D-aspartate (NMDA) antagonists was studied on neonatal rat spinal cord using the grease gap technique. 5,7-Dichlorokynurenate was the most potent and specific glycine site antagonist among the compounds tested. On the other hand mephenesin was a weak non-specific excitatory amino acid (EAA) antagonist; reduction of the response to NMDA was not reversed by D-serine. The EAA antagonist properties of mephenesin could explain its mode of action at the cellular level. The lack of effect of D-serine alone suggests that in our experimental conditions glycine sites on spinal neurones are occupied by an endogenous ligand.
Pralong
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Department of Veterinary Basic Sciences, Royal Veterinary College, London, UK.
Millar
J D
JD
Lodge
D
D
D000818:Animals; D001665:Binding Sites; D005998:Glycine; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008615:Mephenesin / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D011760:Pyrrolidinones / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D007211:Indoles; D011760:Pyrrolidinones; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C075742:5-chloroindole-2-carboxylate; C063295:5,7-dinitroquinoxaline-2,3-dione; D007051:Ibotenic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D008615:Mephenesin; C001369:1-hydroxy-3-amino-2-pyrrolidone; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid; C066192:5,7-dichlorokynurenic acid; D005998:Glycine