nitrous oxide
Approved
Jun 16, 2013
Nitrous oxide (N2O, laughing gas) was first discovered by the English scientist Joseph Priestly and has been used for more than 150 years. It has remained one of the most widely used anesthetics in both dental and medical applications. This small and simple inorganic chemical molecule has indisputable effects of analgesia, anxiolysis, and anesthesia that are of great clinical interest. As a general anesthetic, it is very weak and is generally not used as a single agent. It may be used as a carrier gas with oxygen in combination with more potent general inhalational gases for surgical anesthesia. In dentistry, it is commonly used as a single agent (with oxygen) for partial sedation, most commonly in pediatric dental populations. Findings to date indicate that the analgesic effect of N2O is opioid in nature, and, like morphine, may involve a myriad of neuromodulators in the spinal cord. The anxiolytic effect of N2O, 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 N2O may involve actions at GABA(A) receptors and possibly at N-methyl-D-aspartate receptors as well. — NCATS
Clinical trial activity
179 trials · 157 clinical orgs · 6 marketing orgs
Earliest trial started Sep 1, 1993 (NCT00000249)
Timeline
1790s
- Jun 1, 1794
Evidence of US Marketing
2000s
- Jan 1, 2009
Earliest Phase 1 Sponsor(trial)
2010s
- Jun 16, 2013
Earliest FDA Approval
- Jun 16, 2013
Air Liquide — NDA Secondary Org
- Sep 3, 2013
Nitrous Oxide Corp — First NDA Organization
- Sep 3, 2013
Airgas Usa Llc — NDA Secondary Org
- Sep 3, 2013
Nitrous Oxide Corp — NDA Organization
- Sep 6, 2013
Airgas Usa Llc — Marketing Organization
- Nov 25, 2014
Strata Medical Innovations — NDA Secondary Org
- Jan 9, 2017
Matheson Tri-Gas Inc — NDA Secondary Org
- Mar 6, 2017
Praxair — NDA Secondary Org
Indications
Approved for
Studied for
- Abdominal Neoplasms · Phase 4
- Abortion, Induced · Phase 3
- Abscess · Phase 4
- Acute Coronary Syndrome · Phase 4
- Acute Pain · Phase 4
- Adolescent Health · Phase 2/Phase 3
- Alcohol-Related Disorders · Phase 2
- Amnesia · Early Phase 1
- Analgesia · Phase 4
- Analgesia, Obstetrical · Phase 2/Phase 3
- Anemia, Sickle Cell · Phase 2
- Anesthesia · Phase 4
- Anesthesia, General · Phase 4
- Anesthesia, Obstetrical · Phase 2/Phase 3
- Anesthetics, Inhalation · Phase 1
- Anxiety · Phase 4
- Anxiety Disorders · Phase 4
- Arterial Occlusive Diseases · Phase 2
- Bipolar Disorder · Phase 2
- Brachytherapy · Phase 2
- Bronchoscopy · Phase 3
- Burns · Phase 3
- Bursitis · Phase 4
- Catastrophization · Phase 4
- Cerebral Palsy · Phase 3
- Cesarean Section · Phase 3
- Child · Phase 3
- Colonoscopy · Phase 4
- Colorectal Neoplasms · Phase 3
- Condylomata Acuminata · Phase 2
- Contraceptive Devices · Phase 2/Phase 3
- Coronary Artery Disease · Phase 4
- Dehydration · Phase 3
- Dental Anxiety · Phase 4
- Dental Caries · Phase 3
- Depression · Phase 2
- Depression, Postpartum · Phase 2/Phase 3
- Depressive Disorder · Phase 2
- Depressive Disorder, Treatment-Resistant · Phase 4
- Dermatology · Phase 3
- Dilatation · Early Phase 1
- Disruptive, Impulse Control, and Conduct Disorders · Phase 2
- Drug-Related Side Effects and Adverse Reactions · Phase 4
- Drugs, Investigational · Phase 4
- Elbow · Phase 2
- Electroencephalography · Phase 1
- Endoscopy · Phase 4
- Endothelium · Phase 4
- Epilepsy · Phase 4
- Fibromyalgia · Phase 2
- Glaucoma · Phase 4
- Gynecology · Phase 2/Phase 3
- Headache · Phase 4
- Healthy Volunteers · Phase 4
- Hematologic Neoplasms · Phase 2/Phase 3
- Hemiplegia · Phase 3
- Hydrocephalus · Phase 4
- Hyperalgesia · Phase 1
- Hypertension, Pulmonary · Phase 2
- Injection Site Reaction · Phase 3
- Intraoperative Awareness · Phase 2
- Labor, Obstetric · Phase 3
- Labor Pain · Phase 3
- Lacerations · Phase 4
- Laminaria · Early Phase 1
- Live Birth · Phase 3
- Liver Diseases · Phase 4
- Long-Acting Reversible Contraception · Phase 2/Phase 3
- Lower Urinary Tract Symptoms · Phase 4
- Lung Diseases · Phase 4
- Major Depressive Disorder · Phase 4
- Middle Aged · Phase 4
- Mood Disorders · Phase 1
- Neoplasms · Phase 4
- Neuralgia · Phase 2
- Neurocognitive Disorders · Phase 4
- Neurofibromatoses · Phase 4
- Nitric Oxide · Phase 3
- Nitrous Oxide · Phase 4
- Obsessive-Compulsive Disorder · Phase 2
- Opioid-Related Disorders · Phase 2
- Pain · Phase 4
- Persistent Fetal Circulation Syndrome · Phase 4
- Pharmacological and Toxicological Phenomena · Phase 4
- Pregnancy Complications · Phase 3
- Procedural Pain · Phase 4
- Procedural Sedation · Phase 4
- Prostatic Hyperplasia · Phase 4
- Prostatic Neoplasms · Phase 4
- Psychiatry · Phase 2
- Psychological Distress · Phase 3
- Pulmonary Disease, Chronic Obstructive · Phase 2
- Quadriplegia · Phase 3
- Renal Colic · Phase 2
- Sclerosis · Phase 3
- Spinal Injuries · Phase 4
- Spinal Puncture · Phase 4
- Stress Disorders, Post-Traumatic · Phase 2
- Substance-Related Disorders · Phase 2
- Suicidal Ideation · Phase 2
- Tendinopathy · Phase 2
- Tinea Pedis · Phase 2
- Tinnitus · Phase 4
- Tonsillitis · Phase 2
- Tooth Extraction · Phase 1
- Urinary Incontinence, Stress · Phase 4
- Vasectomy · Early Phase 1
- Vasodilation · Phase 1
- Version, Fetal · Phase 3
- Warts · Phase 2
- Wounds, Nonpenetrating · Phase 4
Mechanism of action
Cannabinoid receptor 1/Mu-type opioid receptor agonist
Approval history
- approvedJun 16, 2013
- approvedJun 1, 1794
Chemistry & pharmacology
SMILES
[O-][N+]#N- Mol. weight
- 44.0128 g/mol
- Lipinski Ro5
- Pass
- Rule of 3
- Yes
- Chirality
- Achiral Molecule
- Inorganic
- No
- Polymer
- No
Oral
No
Parenteral
No
Topical
No
Sources
- WikipediaNitrous oxide (medication) ↗
- NCATSK50XQU1029 ↗
- ChEMBLCHEMBL1234579 ↗
- WikipediaNitrous oxide ↗
Also known as
- dinitrogen monoxide
- dinitrogen oxide
- entonox
- entonox
- nitrious oxide
- nitrious oxide
- nitrious oxide
- nitrous oxide
- nitrous oxide
- nitrous oxide
- nitrous oxide
- nitrous oxide
- nitrous oxide
- nitrous oxide
- nitrous oxide
- nitrous oxide
- nitrous oxide
- nitrous oxide
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT07262008 | Phase 3 | Feb 1, 2026 | Canadian Institutes of Health Research (CIHR), Unity Health Toronto, University of Toronto |
| NCT07245628 | Early Phase 1 (Phase 1) | Oct 20, 2025 | Harvard University |
| NCT07118644 | Phase 3 | Sep 1, 2025 | University of Western Brittany |
| NCT06702631 | Early Phase 1 (Phase 1) | Feb 1, 2025 | National Institute of General Medical Sciences (NIGMS), University of Pittsburgh |
| NCT06557642 | N/A | Jul 10, 2024 | University of Oxford |
| NCT06430489 | Phase 2 | Jun 30, 2024 | University Hospital, Tours |
| NCT06498908 | Phase 3 | May 15, 2024 | Maimonides Medical Center |
| NCT05890898 | N/A | Sep 19, 2023 | Geisinger Clinic |
| NCT05710887 | Phase 2 | Jul 1, 2023 | University of Chicago |
| NCT05178849 | N/A | Jun 1, 2023 | University of Rennes |
| NCT05895383 | Phase 4 | May 24, 2023 | Harvard University |
| NCT05883332 | Phase 4 | Jan 10, 2023 | Harvard University |
| NCT05579288 | Early Phase 1 (Phase 1) | Dec 31, 2022 | Tel Aviv University |
| NCT05388942 | N/A | Nov 30, 2022 | University of Reims |
| NCT05383495 | Phase 3 | Oct 1, 2022 | University of Western Ontario |
| NCT06118567 | Phase 2 | Sep 6, 2022 | National Institute of Mental Health (NIMH), Ohio State University |
| NCT05396144 | Phase 4 | Aug 31, 2022 | Stanford University |
| NCT05510141 | N/A | Aug 24, 2022 | University of Bern |
| NCT05430750 | Phase 4 | Jun 29, 2022 | Sir Ganga Ram Hospital |
| NCT05167331 | N/A | Feb 28, 2022 | University of Strasbourg |
Organizations
Research & Development (157)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| University of Chicago | Academic/Hospital | 19 | 19 | 2 | 1993 |
| National Institute on Drug Abuse (NIDA) | Government | 16 | 0 | 2 | 1993 |
| Washington University in St. Louis | Academic/Hospital | 8 | 8 | 4 | 2008 |
| Air Liquide | For profit | 7 | 6 | 4 | 2000 |
| Harvard University | Academic/Hospital | 6 | 6 | 4 | 2014 |
| Monash University | Academic/Hospital | 6 | 3 | 2 | 2003 |
| Yeshiva University | Academic/Hospital | 5 | 4 | 2 | 2013 |
| Stanford University | Academic/Hospital | 4 | 4 | 3 | 2018 |
| The Alfred Hospital | Academic/Hospital | 4 | 0 | 2 | 2003 |
| University of New Mexico | Academic/Hospital | 4 | 4 | 1 | 2012 |
| University of Paris | Academic/Hospital | 4 | 3 | 2 | 2008 |
| University of Toulouse | Academic/Hospital | 4 | 4 | 3 | 2010 |
| Ohio State University | Academic/Hospital | 3 | 3 | 2 | 2012 |
| Society of Family Planning | Academic/Hospital | 3 | 0 | 1 | 2013 |
| Tel Aviv University | Academic/Hospital | 3 | 3 | 2 | 2014 |
| University Clermont Auvergne | Academic/Hospital | 3 | 3 | 1 | 2014 |
| University of Colorado, Denver | Academic/Hospital | 3 | 1 | 2 | 2016 |
| University of Lyon | Academic/Hospital | 3 | 2 | 3 | 2006 |
| University of Rochester | Academic/Hospital | 3 | 3 | 2 | 1998 |
| University of Toronto | Academic/Hospital | 3 | 3 | 3 | 2015 |
Marketing (7)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| Air Liquide | For profit | NDA2 | Jun 16, 2013 |
| Airgas Usa Llc | For profit | NDA2 | Sep 3, 2013 |
| Airgas Usa Llc | For profit | MKTG | Sep 6, 2013 |
| Matheson Tri-Gas Inc | For profit | NDA2 | Jan 9, 2017 |
| Nitrous Oxide Corp | For profit | NDA | Sep 3, 2013 |
| Praxair | For profit | NDA2 | Mar 6, 2017 |
| Strata Medical Innovations | For profit | NDA2 | Nov 25, 2014 |