Synergism between the NMDA receptor antagonistic effects of ifenprodil and the glycine antagonist, 7-chlorokynurenate, in vivo.
Ifenprodil (30 mg/kg i.p.) when administered alone did not antagonise the stimulatory effects of intrastriatally administered N-methyl-D-aspartate (NMDA: 500 microM, via a dialysis fibre) on spermine or spermidine release. The effects of NMDA were antagonised by the intrastriatal co-infusion of the glycine site antagonist, 7-chlorokynurenate (100 microM). Lower concentrations of 7-chlorokynurenate (3 microM) were without effect on the NMDA response. In the presence of a subthreshold concentration of striatally infused 7-chlorokynurenate (3 microM), systemically administered ifenprodil (30 mg/kg i.p.) blocked the effects of NMDA on polyamine release and also potentiated the inhibitory effects of 30 microM 7-chlorokynurenate. These results demonstrate that synergism between glycine antagonists and polyamine antagonists, as previously observed in vitro, is also observed in vivo.
Synthelabo Recherche (L.E.R.S.), Department of Neurochemistry II, Rueil-Malmaison, France.
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Voltz
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Fage
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Carter
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004357:Drug Synergism; D005998:Glycine / Q000037:antagonists & inhibitors*; D007267:Injections; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017072:Neostriatum; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism
D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D013096:Spermine; D016202:N-Methylaspartate; D007736:Kynurenic Acid; C010739:ifenprodil; C057013:7-chlorokynurenic acid; D005998:Glycine; D013095:Spermidine