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.