NMethylDAspartate Antagonists

Research implicates the excitatory neurotransmitter glutamate in the development of central sensitization and the maintenance of chronic pain. Some evidence suggests that N-methyl-D-aspartate (NMDA) antagonists, i.e., dextromethorphan, ketamine, memantine, and amanta-dine, may have a role in mitigating chronic pain, including neuropathy, chronic phantom pain, fibromyalgia, and in cases of pain associated with spinal cord injury (Fisher et al. 2000, Sang et al. 2002). However, the analgesic effects in various trials have demonstrated inconsistent results (Eisenberg et al. 1998, Enarson et al. 1999).

The side effects associated with the NMDA antagonists include sedation, dry mouth, headache, and constipation; in some cases these effects can be prohibitively severe limiting usefulness (Eide et al. 1994). For example, ketamine is a dissociative anesthetic producing hallucinations, frightening nightmares, and delirium. These effects can be avoided when low doses are employed, e.g., 50-60 mg four to six times daily. The place of ketamine and other NMDA antagonists in the treatment of chronic pain and the effects of long-term use remain unclear (Brown and Krupp 2006, Visser and Schug 2006).

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