the effect of dehydroepiandrosterone sulfate and allopregnanolone sulfate on the binding of 3hifenprodil to the nmethyldaspartate receptor in rat frontal cortex membrane neurosteroids have been shown to modulate the nmethyldaspartate nmda receptor function dehydroepiandrosterone sulfate dheas is shown to participate in memory and learning processes as well as preventing glutamate neurotoxicity in hippocampus in this study we have focused on the modulatory effect of neurosteroids on ifenprodil binding to the nr2b subunit of the nmda receptor we show that dheas and allopregnanolone sulfate allopregs exert different effects on the 3hifenprodil binding at 10 30 or 100 nm corresponding to physiological concentrations the effects include changes in the ifenprodil displacement curve changing it from a onesite fit into a twosite fit leaving bmax kd and koff unaffected our results indicate that dheas and allopregs induce an allosteric modulation of the nmda receptor an observation that might contribute to the understanding of the effects of these neurosteroids