[12] The first devices used in dentistry to administer the gas consisted of a simple breathing bag made of rubber cloth.

It was not until 1961 that the first paper was published by Michael Tunstall and others, describing the administration of a pre-mixed 50:50 nitrous oxide and oxygen mix, which led to the commercialisation of the product.

[11] In 1970, Peter Baskett recognised that pre-mixed nitrous oxide and oxygen mix could have an important part to play in the provision of pre-hospital pain relief management, provided by ambulance personnel.

[14] Today the nitrous oxide is administered in hospitals by a relative analgesia machine, which includes several improvements such as flowmeters and constant-flow regulators, an anaesthetic vaporiser, a medical ventilator, and a scavenger system, and delivers a precisely dosed and breath-actuated flow of nitrous oxide mixed with oxygen.

[1] It is removed from the body unchanged via the lungs, and does not accumulate under normal conditions, explaining the rapid offset of around 60 seconds.

Its analgesic effect is strong (equivalent to 15 mg of subcutaneous route morphine[1])[17][18] and characterised by rapid onset and offset, i.e. it is very fast-acting and wears off very quickly.

[citation needed] When used in combination with other anesthetics gases, nitrous oxide causes a dose dependent increased respiratory rate and decreased tidal volumes, the net effect is a lower minute ventilation.

[23] Self-administration of Entonox is safe because if enough is inhaled to start to induce anaesthesia, the patient becomes unable to hold the valve, and so will drop it and soon exhale the residual gas.

However, it has been shown to directly modulate a broad range of ligand-gated ion channels, and this likely plays a major role in many of its effects.

[27] While N2O affects quite a few ion channels, its anesthetic, hallucinogenic and euphoriant effects are likely caused predominantly, or fully, via inhibition of NMDA receptor-mediated currents.

[25][28] In addition to its effects on ion channels, N2O may act to imitate nitric oxide (NO) in the central nervous system, and this may be related to its analgesic and anxiolytic properties.

Nitronox was a registered trademark of the BOC Group between 1966 and 1999,[29] and was reregistered by Hs Tm Inc since 2005[citation needed] It is also colloquially known as "gas and air" in the United Kingdom.