, Volume 102, Issue 4, pp 551–552 | Cite as

Effect of NMDA- and strychnine-insensitive glycine site antagonists on NMDA-mediated convulsions and learning

  • Christian Chiamulera
  • Silvano Costa
  • Angelo Reggiani
Rapid Communications


Intracerebroventricular (ICV) injection of N-methyl-d-aspartate (NMDA) was shown to induce generalized seizures in mice. The competitive NMDA antagonistsdl-2-amino-5-phosphonovaleroate (dl-AP7) and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), the NMDA “channel blocker” antagonist (+)-5-methyl-10,11-dihydro 5H-dibenzo-[a,d] cycloheptan-5,10-imine maleate (MK-801) and the strychnine-insensitive glycine antagonists kynurenic acid (KYNA) and 7-chloro-kynurenic acid (7-Cl-KYNA), when co-administered (ICV) with NMDA, antagonized NMDA-induced generalized seizures. Administration (ICV) ofdl-AP7, CPP and MK-801 resulted in impared learning performance in a passive avoidance task in mice, with ED50 close to the anticonvulsant dose. The glycine antagonists KYNA and 7-Cl-KYNA at high doses significantly failed to affect performance in the same model of learning. The results indicate that compounds acting at the strychnine-insensitive glycine site may have a larger “therapeutic window” as anticonvulsants than antagonists of the NMDA receptor and channel.

Key words

NMDA receptor antagonists Glycine antagonists Convulsions Learning 


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Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Christian Chiamulera
    • 1
  • Silvano Costa
    • 1
  • Angelo Reggiani
    • 1
  1. 1.Glaxo Research LaboratoriesVeronaItaly

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