Age-related decrease in the antiseizure effect of ifenprodil against pentylenetetrazole in mice

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.