Ifenprodil and a group of related compounds are selective antagonists of NR
2B-containing NMDA receptors. These compounds are antinociceptive in a vari
ety of preclinical pain models and have a much lower side-effect profile co
mpared with other NMDA receptor antagonists. It remains unclear whether the
improved safety of these compounds is due to their subtype selectivity or
to a unique mode of inhibition of the receptor. Human trials have so far co
nfirmed the good tolerability of these subtype-selective NMDA receptor anta
gonists; however, whether they are as effective as other NMDA receptor anta
gonists in pain patients remains to be demonstrated.