N-methyl-D-aspartate- enhanced analgesia

A greater understanding of the mechanisms that produce chronic pain states has led to a search for novel agents with the potential to produce analgesia by directly modulating specific processes involved in the transduction, transmission, modulation, perception, and encoding of pain. It is hoped that compounds directed at these specific targets will produce better analgesics with an improved side-effect profile. The N-methyl-D-aspartate receptor has been shown to play an important role in pain modulation and has become a target for potential analgesic compounds. Antagonists to the N-methyl-D-aspartate receptor were antinociceptive in a number of animal models, and analgesic in experimental pain models in healthy subjects and in chronic neuropathic pain syndromes. In addition, these compounds have demonstrated the ability to prevent the development of tolerance to opioid analgesic therapy. This has led to investigations of therapies that combine an opioid agonist with an N-methyl-D-aspartate receptor antagonist.