Medications and Pharmacology: What Drugs Are Similar to Nitrous Oxide?

October 8, 2025 •

2 min read

Used for over 150 years in clinical settings, nitrous oxide, also known as "laughing gas," is a common anesthetic and analgesic. The question of what drugs are similar to nitrous oxide arises from its specific clinical applications, limitations, and unique pharmacological properties that rely on its rapid onset and offset.

Quick Summary

This article explores pharmacological agents sharing similarities with nitrous oxide, examining dissociative anesthetics like ketamine and xenon. It details their comparative uses, mechanisms of action, and clinical differences, offering insight into alternatives for sedation and analgesia.

Key Points

NMDA Antagonism: Key alternatives like ketamine and xenon share nitrous oxide's primary mechanism of action by antagonizing NMDA receptors, leading to dissociative and anesthetic effects.
Ketamine is a more potent dissociative: Ketamine provides stronger analgesia and more profound dissociation than N2O but has a longer duration of action and higher abuse potential.
Xenon is a potent alternative: The noble gas xenon is a more potent analgesic than N2O, offers high cardiovascular stability, and works via NMDA antagonism, but its use is limited by very high costs.
Different Mechanisms for Other Sedatives: Many sedatives and general anesthetics, such as propofol, midazolam, and volatile agents, work primarily by modulating GABAA receptors rather than NMDA receptors, resulting in different clinical effects.
Inhalational vs. Intravenous: The route of administration is a major difference, with N2O and xenon being inhalational gases while ketamine can be given via IV or other routes, impacting onset, offset, and duration of effect.
Unique Therapeutic Uses: Beyond anesthesia, N2O and ketamine are being investigated for similar uses in treating treatment-resistant depression, highlighting their comparable psychotropic actions.

Understanding Nitrous Oxide's Pharmacological Profile

Nitrous oxide (N2O) is an inhaled gas used for its pain-relieving (analgesic), anxiety-reducing (anxiolytic), and memory-impairing (amnestic) effects, often alongside more potent anesthetics. Its quick absorption and elimination lead to a fast onset and recovery.

Nitrous oxide primarily works by blocking NMDA receptors in the central nervous system, reducing excitatory signals. It also affects the opioid and noradrenergic systems, contributing to pain relief. As a weak anesthetic, it's typically used in combination with other agents.

Dissociative Anesthetics: Ketamine and its Analogues

Ketamine is a dissociative anesthetic that, like nitrous oxide, primarily blocks NMDA receptors. This shared mechanism results in similar psychotomimetic and rapid antidepressant effects. However, ketamine is different in its strength, duration, and how it is given. For key characteristics of ketamine, refer to {Link: DrOracle.ai https://www.droracle.ai/articles/132117/inhaled-nitrous-oxide-vs-ketamine-moa}. Other dissociatives with similar effects at high doses include Dextromethorphan (DXM) and Methoxetamine.

The Noble Gas Alternative: Xenon

Xenon is another inhaled gas that blocks NMDA receptors. As a noble gas, xenon is a more potent pain reliever and anesthetic than nitrous oxide. For xenon's notable properties, refer to {Link: DrOracle.ai https://www.droracle.ai/articles/132117/inhaled-nitrous-oxide-vs-ketamine-moa}.

Comparison of Alternatives to Nitrous Oxide


Feature	Nitrous Oxide	Ketamine	Xenon
Mechanism	Noncompetitive NMDA antagonism.	Noncompetitive NMDA antagonism.	Noncompetitive NMDA antagonism.
Onset/Offset	Very rapid, within minutes.	Variable depending on route; longer than N2O.	Rapid onset/offset, similar to N2O.
Potency (Anesthetic)	Weak; requires high concentrations or adjuncts.	Strong; can be used as a sole anesthetic.	Moderately potent; can be used alone.
Potency (Analgesic)	Moderate.	Strong.	Stronger than N2O.
Route of Admin.	Inhalation via mask.	IV, IM, intranasal, or oral.	Inhalation via mask.
Primary Use	Adjunct anesthetic, procedural sedation.	General anesthesia, depression treatment.	General anesthesia.
Cost	Low	Moderate	Very high.
Major Side Effects	Nausea, B12 inhibition with long exposure.	Dissociation, increased BP, nausea, abuse potential.	Euphoria/dysphoria, nausea.

Other Sedatives and Anesthetics

Other drugs provide similar effects through different mechanisms. These include:

Intravenous Sedatives: Propofol and midazolam are IV sedatives that act by enhancing GABAA receptors, unlike N2O's NMDA action. Dexmedetomidine is another IV option with sedative and analgesic properties.
Volatile Anesthetics: Inhaled liquids like isoflurane and sevoflurane are more potent general anesthetics than N2O and work on GABAA receptors.
Opioid Analgesics: Opioids offer strong pain relief and sedation, partly overlapping with N2O's effects via the opioid system. However, opioids carry risks like respiratory depression and addiction.

Conclusion

Nitrous oxide is valuable in medicine, and several other agents share or overlap its properties. Ketamine is a more potent dissociative with a similar NMDA blocking mechanism but differs in duration and side effects. Xenon offers better pain relief and cardiovascular stability but is very expensive. Other sedatives and anesthetics like propofol and sevoflurane work differently, primarily on GABAA receptors. For further reading on anesthetic gases, the {Link: NCBI Bookshelf https://www.ncbi.nlm.nih.gov/books/NBK537013/} is a valuable resource.

Frequently Asked Questions

Both ketamine and nitrous oxide primarily act as noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor, which explains their overlapping dissociative, analgesic, and psychotropic effects.

Xenon is a viable and, in some ways, superior alternative to nitrous oxide, offering more potent analgesia and excellent cardiovascular stability. However, its widespread use is currently limited due to its extremely high cost.

While nitrous oxide primarily works on NMDA receptors, general anesthetics like propofol and isoflurane act mainly by modulating GABAA receptors, resulting in deeper sedation and different side effect profiles. Nitrous oxide is also less potent and often used as an adjunct.

Yes, drugs like ketamine can be administered intravenously and provide similar dissociative, analgesic, and anxiolytic effects, though with a longer duration of action and higher potency.

The 'second gas effect' is a phenomenon where the rapid uptake of a primary gas like nitrous oxide accelerates the uptake of a concurrently administered second gas. This effect contributes to a faster induction of anesthesia when N2O is combined with other volatile agents.

One potential side effect of prolonged or repeated nitrous oxide exposure is the inactivation of vitamin B12, which can lead to neurological issues and megaloblastic anemia. This is a unique consideration compared to other agents.

Dexmedetomidine is an intravenous sedative with analgesic properties, whereas nitrous oxide is an inhaled gas. While they can be used together and synergize, dexmedetomidine is sometimes seen as a safer alternative due to fewer environmental concerns and a lack of long-term side effects associated with N2O.