The developmental change in the antiseizure effect of ifenprodil against pentylenetetrazole (PTZ) was examined in mice. Ifenprodil (i.p.) significantly increased the latency to seizure induced by PTZ in 7- and 10- day-old mice, but not in 14- or 21-day-old mice. Intracerebroventricular administration of ifenprodil also failed to modify the latency to PTZ- induced seizure in 21-day-old mice. Dizocilpine produced an increase in the latency to PTZ-induced seizure in 7- and 21-day-old mice. In an NMDA receptor binding assay using [3H]dizocilpine, ifenprodil was clearly more potent in inhibiting [3H]dizocilpine binding in a forebrain membrane preparation from 7- rather than 21-day-old mice. These results suggest that the remarkable antiseizure effect of ifenprodil against PTZ in 7-day-old mice may be related to the high proportion of ifenprodil-sensitive NMDA receptors in the brain.
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