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

Area of Science:

• Neuroscience
• Developmental Biology
• Pharmacology

Background:

• The antiseizure effects of drugs can vary significantly with age.
• N-methyl-D-aspartate (NMDA) receptors play a crucial role in neuronal excitation and seizure generation.
• Ifenprodil is a known antagonist of certain NMDA receptor subtypes.

Purpose of the Study:

• To investigate the developmental changes in the antiseizure efficacy of ifenprodil.
• To explore the relationship between ifenprodil's effect and NMDA receptor sensitivity during early development.

Main Methods:

• Administering ifenprodil intraperitoneally and intracerebroventricularly to mice of different ages (7, 10, 14, and 21 days old).
• Inducing seizures using pentylenetetrazole (PTZ) and measuring the latency to seizure onset.
• Conducting NMDA receptor binding assays using [3H]dizocilpine to assess ifenprodil's binding affinity in brain preparations from different age groups.

Main Results:

• Ifenprodil significantly increased seizure latency in 7- and 10-day-old mice but not in older mice.
• Intracerebroventricular administration of ifenprodil did not alter seizure latency in 21-day-old mice.
• Ifenprodil demonstrated higher potency in inhibiting [3H]dizocilpine binding in brain membranes from 7-day-old mice compared to 21-day-old mice.
• Dizocilpine showed an increase in seizure latency in both 7- and 21-day-old mice.

Conclusions:

• The antiseizure effect of ifenprodil against PTZ-induced seizures is age-dependent, being more pronounced in younger mice.
• The developmental decrease in ifenprodil's efficacy correlates with reduced sensitivity of NMDA receptors to ifenprodil.
• These findings suggest that the proportion of ifenprodil-sensitive NMDA receptors in the brain influences its antiseizure activity during development.