When one compound in a chemical class has problems, it's no big deal. When two do, eyebrows begin to rise. When three do, it may be time to rethink the target.
Further complicating the issue is the complexity of some of the indications targeted by NMDA antagonists. Cerestat and related compounds are intended to prevent neuronal injury by preventing glutamate-induced calcium influx into neurons. This influx is thought to occur primarily through the NMDA-receptor ion channel, leading to over-excitement and death of neurons.
The appeal of this targeting strategy is that activation of NMDA channels is thought to be essential in leading to neuronal death after stroke