Advances in understanding the actions of nitrous oxide.

Nitrous oxide (N(2)O) has been used for well over 150 years in clinical dentistry for its analgesic and anxiolytic properties. This small and simple inorganic chemical molecule has indisputable effects of analgesia, anxiolysis, and anesthesia that are of great clinical interest. Recent studies have helped to clarify the analgesic mechanisms of N(2)O, but the mechanisms involved in its anxiolytic and anesthetic actions remain less clear. Findings to date indicate that the analgesic effect of N(2)O is opioid in nature, and, like morphine, may involve a myriad of neuromodulators in the spinal cord. The anxiolytic effect of N(2)O, on the other hand, resembles that of benzodiazepines and may be initiated at selected subunits of the gamma-aminobutyric acid type A (GABA(A)) receptor. Similarly, the anesthetic effect of N(2)O may involve actions at GABA(A) receptors and possibly at N-methyl-D-aspartate receptors as well. This article reviews the latest information on the proposed modes of action for these clinical effects of N(2)O.