NMDA-Receptor antagonists in neuropathic pain: Experimental methods to clinical trials

Recent clinical data suggest that chronic pain due to ne,ve or soft tissue injury may result in the sensitization of the central nervous system, media ted in part by the excitatory amino acids, glutamate and aspartate. Only a handful of N-methyl-D-aspartate antagonists are clinically available. These include ketamine, dextromethorphan, memantine, and amantadine, as well as three clinically used opioids (methadone, dextropropoxyphene, and ketobemid one). This review summarizes the single-dose efficacy of the first two comp ounds in the treatment of experimental and neuropathic pain. In all example s presented here, NMDA-receptor antagonists with affinity at the phencyclid ine site have been shown to modulate pain and hyperalgesia but are limited by dose-limiting side effects. Thus, provided their therapeutic ratio is fa vorable, NMDA-receptor antagonists may be effective in the treatment of som e types of chronic pain. J Pain Symptom Manage 2000;19:S21-S25. (C) U.S. Ca ncer Pain Relief Committee, 2000.