N2O

Oral🕒 Plan

Route dataTripSit

Mechanism of actionPH

Findings to date indicate that nitrous oxide induces opioid peptide release in the brain stem leading to the activation of descending noradrenergic neurones, which results in modulation of the nociceptive process in the spinal cord. Several receptor–effector mechanisms including dopamine receptors, α2 adrenoceptors, benzodiazepine receptors and -methyl- -aspartate (NMDA) receptors have been implicated although the relationship of one with the other is not known.
Nitrous oxide (N2O) gas is a widely used anesthetic adjunct in dentistry and medicine that is also commonly abused. Studies have shown that N2O alters the function of the N-methyl-d-aspartate (NMDA), GABAA, opioid, and serotonin receptors among others. However, the receptors systems underlying the abuse-related central nervous system effects of N2O are unclear. The present study explores the receptor systems responsible for producing the discriminative stimulus effects of N2O. B6SJLF1/J male mice trained to discriminate 10 minutes of exposure to 60% N2O + 40% oxygen versus 100% oxygen served as subjects. Both the high-affinity NMDA receptor channel blocker (+)-MK-801 maleate [(5S,10R)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] and the low-affinity blocker memantine partially mimicked the stimulus effects of N2O. Neither the competitive NMDA antagonist, CGS-19755 (cis-4-[phosphomethyl]-piperidine-2-carboxylic acid), nor the NMDA glycine-site antagonist, L701-324 [7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(1H)-quinolinone], produced N2O-like stimulus effects. A range of GABAA agonists and positive modulators, including midazolam, pentobarbital, muscimol, and gaboxadol (4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol), all failed to produce N2O-like stimulus effects. The mu-, kappa-, and delta-opioid agonists, as well as 5-hydroxytryptamine (serotonin) 1B/2C (5-HT1B/2C) and 5-HT1A agonists, also failed to produce N2O-like stimulus effects. Ethanol partially substituted for N2O. Both (+)-MK-801 and ethanol but not midazolam pretreatment also significantly enhanced the discriminative stimulus effects of N2O. Our results support the hypothesis that the discriminative stimulus effects of N2O are at least partially mediated by NMDA antagonist effects similar to those produced by channel blockers. However, as none of the drugs tested fully mimicked the stimulus effects of N2O, other mechanisms may also be involved.
N2O interferes with vitamin B12 and folate metabolism. This impairs production of methionine (from homocysteine), used to form tetrahydrofolate and thymidine during DNA synthesis.
Nitrous oxide is 35 times more soluble than nitrogen. The gas exchanges with nitrogen and diffuses into hollow viscera and body spaces potentially containing air, such as pneumothorax, paranasal sinuses and pneumoperitoneum, or into the cerebral ventricles following pneumoencephalography. This expands the body of trapped air and increases the pressure within such closed spaces. When administration is discontinued, nitrous oxide is released into the alveoli, diluting the alveolar gases. A reduction in alveolar oxygen tension may result. This is referred to as diffusion anoxia. Because of the high concentration of nitrous oxide required to produce and maintain anesthesia, hypoxia is an unavoidable accompaniment to its use. During induction with high concentrations of nitrous oxide, the oxygen in the lungs is rapidly used up and the anoxia with increased respiratory effort causes rapid depletion of carbon dioxide in the tissues. Absence of carbon dioxide and depression of the medullary centers by the anesthetic quickly lead to respiratory failure, and rarely, the patient's cerebral function fails to recover from cerebral damage caused by the prolonged anoxia. The brain suffers anoxia from the very beginning of the administration of the gas, and not from just the moment of cessation of respiratory movements. Thus, the period of anoxia may be five minutes or more, sufficient to cause permanent brain damage in the susceptible individual. The arbitrary "safe period" of eight minutes may be too long for some patients.
Nitrous oxide induces inconsistent changes in the basal levels of the thalamic nuclei. The mechanism of analgesia is believed to involve a direct intraspinal anti-nociceptive action rather than depression of limbic function. In the brain stem, responses evoked by pain stimulation are depressed, although the extent of depression may be variable. Nitrous oxide in anesthetic doses increases cerebral blood flow and intracranial pressure.
For more Mechanism of Action (Complete) data for Nitrous oxide (7 total), please visit the HSDB record page.

Pharmacokinetics

External links