Nitrous oxide has been used therapeutically as an anesthetic and an analgesic for more than 100 years. The anesthetic effect is thought to be mediated primarily by the reversible inhibition of the N-methyl-d-aspartate type of glutamate receptors resulting in inhibition of excitatory glutamatergic neurotransmission. Nitrous oxide exerts it analgesic effects via activation of opioidergic neurons. Most significant human exposure to nitrous oxide occurs in medical settings either by therapeutic administration or as unintended exposure:
