nitric oxide
Trade name: inomax
Approved
Dec 23, 1999
In mammals Nitric Oxide (NO) is an important cellular signaling molecule involved in many physiological and pathological processes. It is a powerful vasodilator with a short half-life of a few seconds in the blood. Low levels of nitric oxide production are important in protecting organs such as the liver from ischemic damage. Nitric oxide production is associated with nonalcoholic fatty liver disease (NAFLD) and is essential for hepatic lipid metabolism under starvation. Nitric oxide (INOmax) is indicated to improve oxygenation and reduce the need for extracorporeal membrane oxygenation in term and near-term (>34 weeks gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension in conjunction with ventilatory support and other appropriate agents. Nitric oxide relaxes vascular smooth muscle by binding to the heme moiety of cytosolic guanylate cyclase, activating guanylate cyclase and increasing intracellular levels of cyclic guanosine 3',5'-monophosphate, which then leads to vasodilation. When inhaled, nitric oxide selectively dilates the pulmonary vasculature, and because of efficient scavenging by hemoglobin, has minimal effect on the systemic vasculature. INOmax appears to increase the partial pressure of arterial oxygen (PaO2) by dilating pulmonary vessels in better-ventilated areas of the lung, redistributing pulmonary blood flow away from lung regions with low ventilation/perfusion (V/Q) ratios toward regions with normal ratios. NO, can be generated in large quantities and has detrimental effects on the CNS. NO has been shown to increase permeability of the BBB, allowing substances to enter into the brain passively. Because of its importance in neuroscience, physiology, and immunology, NO was proclaimed "Molecule of the Year" in 1992. Research into its function led to the 1998 Nobel Prize for discovering the role of nitric oxide as a cardiovascular signaling molecule (Furchgott, Murad and Ignarro). — NCATS
Clinical trial activity
192 trials · 178 clinical orgs · 8 marketing orgs
Earliest trial started Apr 4, 1992 (NCT00001303)
Timeline
1990s
- Jan 1, 1992
Earliest Phase 1 Sponsor(trial)
- Jun 22, 1993
Orphan Drug Designation
- Jan 1, 1995
Earliest Phase 3 Sponsor(trial)
- Jan 1, 1998
Earliest Phase 2 Sponsor(trial)
- Dec 23, 1999
INO Therapeutics — Earliest FDA Approval
- Dec 23, 1999
INO Therapeutics — NDA Organization
- Dec 23, 1999
Mallinckrodt — NDA Secondary Org
- Dec 23, 1999
International Minerals and Chemical Corporation — NDA Secondary Org
- Dec 23, 1999
Mallinckrodt — Marketing Organization
2010s
- Oct 2, 2018
Praxair — Marketing Organization
- Oct 2, 2018
Linde AG — Marketing Organization
- Oct 2, 2018
BOC International — Marketing Organization
- Dec 20, 2019
Vero Biotech — Marketing Organization
- Dec 20, 2019
Vero Biotech — NDA Secondary Org
2020s
- Jul 27, 2023
AIRGAS THERAP — Marketing Organization
Indications
Studied for
- Acidosis, Respiratory · Phase 1/Phase 2
- Acute Chest Syndrome · Phase 2/Phase 3
- Acute Kidney Injury · Phase 4
- Anemia · Phase 1/Phase 2
- Anemia, Sickle Cell · Phase 2/Phase 3
- Aortic Dissection · Phase 4
- Asthma · Phase 4
- Biomarkers · Phase 2
- Blood Platelet Disorders · Phase 2/Phase 3
- Blood Transfusion · Phase 2
- Brain Injuries, Traumatic · Phase 3
- Bronchiolitis · Phase 3
- Bronchopulmonary Dysplasia · Phase 3
- Candidiasis, Oral · Phase 1
- Cardiac Output, Low · Phase 3
- Cardiomyopathies · Phase 3
- Cardiopulmonary Bypass · Phase 3
- Cardiovascular Diseases · Phase 2
- Cerebral Intraventricular Hemorrhage · Phase 2/Phase 3
- Cerebrovascular Disorders · Phase 1
- Cerebrovascular Trauma · Phase 1
- Chest Pain · Phase 2
- Child Behavior · Phase 3
- Colorectal Neoplasms · Phase 1
- Coronary Artery Bypass · Phase 1/Phase 2
- Coronary Artery Disease · Phase 1/Phase 2
- Coronary Disease · Phase 2
- Coronavirus · Phase 2
- Coronavirus Infections · Phase 2
- COVID-19 · Phase 3
- Critical Illness · Early Phase 1
- Cross Infection · Phase 2
- Cystic Fibrosis · Phase 2
- Diabetic Foot · Phase 3
- Dyspnea · Phase 2
- Electroencephalography · Phase 2
- Endothelial Cells · Phase 2
- Endothelium · Phase 2
- Familial Primary Pulmonary Hypertension · Phase 3
- Fontan Procedure · Phase 3
- Gastroesophageal Reflux · Phase 1
- General Surgery · Phase 3
- Healthy Volunteers · Phase 2
- Heart Arrest · Phase 2
- Heart Defects, Congenital · Phase 3
- Heart Disease Risk Factors · Phase 2
- Heart Diseases · Phase 3
- Heart Failure · Phase 4
- Heart Transplantation · Phase 2
- Heart Valve Diseases · Phase 1/Phase 2
- Hemolysis · Phase 2
- Hernias, Diaphragmatic, Congenital · Phase 4
- Hypertension, Pulmonary · Phase 4
- Hypertrophy, Left Ventricular · Phase 2
- Hypoxia · Phase 3
- Hypoxia-Ischemia, Brain · Phase 1/Phase 2
- Idiopathic Pulmonary Fibrosis · Phase 2
- Infant · Phase 4
- Infant, Low Birth Weight · Phase 3
- Infant, Newborn · Phase 3
- Infant, Premature · Phase 3
- Infant, Premature, Diseases · Phase 2/Phase 3
- Infant, Small for Gestational Age · Phase 3
- Inflammation · Phase 2/Phase 3
- Leg Ulcer · Phase 1/Phase 2
- Leishmaniasis, Cutaneous · Phase 3
- Leukomalacia, Periventricular · Phase 2/Phase 3
- Liver Diseases · Phase 2/Phase 3
- Lung Diseases · Phase 3
- Lung Transplantation · Phase 2
- Malaria · Phase 1/Phase 2
- Malaria, Cerebral · Phase 2
- Methicillin-Resistant Staphylococcus aureus · Phase 2
- Molluscum Contagiosum · Phase 3
- Mycobacterium Infections, Nontuberculous · Phase 2
- Myocardial Infarction · Phase 2
- Myocardial Ischemia · Phase 2
- Myocardial Reperfusion Injury · Phase 1/Phase 2
- Neoplasms · Phase 1
- Neuralgia · Phase 2
- Nitric Oxide · Phase 3
- Nitrous Oxide · Phase 4
- Out-of-Hospital Cardiac Arrest · Phase 2
- Oxidative Stress · Phase 2
- Oxygen Saturation · Phase 2
- Pain · Phase 4
- Persistent Fetal Circulation Syndrome · Phase 4
- Pneumonia · Phase 3
- Pneumonia, Aspiration · Phase 3
- Pneumonia, Viral · Phase 2
- Postoperative Complications · Phase 2
- Prehypertension · Phase 1/Phase 2
- Premature Birth · Phase 4
- Pressure Ulcer · Phase 1/Phase 2
- Psoriasis · Phase 1
- Pulmonary Arterial Hypertension · Phase 3
- Pulmonary Diffusing Capacity · Phase 1
- Pulmonary Disease, Chronic Obstructive · Phase 2
- Pulmonary Embolism · Phase 2
- Pulmonary Fibrosis · Phase 2
- Renal Insufficiency, Chronic · Phase 1/Phase 2
- Reperfusion Injury · Phase 3
- Respiratory Distress Syndrome · Phase 3
- Respiratory Distress Syndrome, Newborn · Phase 3
- Respiratory Insufficiency · Phase 4
- Respiratory Tract Infections · Phase 2
- Retinopathy of Prematurity · Phase 3
- Sarcoidosis, Pulmonary · Phase 2
- Sepsis · Phase 3
- Severe Acute Respiratory Syndrome · Phase 2
- Shock, Septic · Phase 1
- Sinusitis · Phase 2
- Skin Ulcer · Phase 2
- ST Elevation Myocardial Infarction · Phase 2
- Stroke · Phase 2
- Suicidal Ideation · Phase 2
- Suicide · Phase 2
- Thoracic Surgery · Phase 3
- Tinea · Phase 2
- Tinea Pedis · Phase 2
- Transposition of Great Vessels · Phase 3
- Ulcer · Phase 2
- Varicose Ulcer · Phase 2
- Vasoconstriction · Phase 1
- Ventricular Dysfunction, Left · Phase 3
- Walk Test · Phase 2
- Warts · Phase 2
Mechanism of action
- Soluble guanylate cyclaseACTIVATOR
Soluble guanylate cyclase activator
Heterodimer, beta (1 or 2) is binding site
Approval history
- approvedPriority reviewDec 23, 1999
Chemistry & pharmacology
SMILES
[N]=O- Mol. weight
- 30.0061 g/mol
- Lipinski Ro5
- Pass
- Rule of 3
- Yes
- Chirality
- Achiral Molecule
- Inorganic
- No
- Polymer
- No
- Delivery
- Topical
- Availability
- Prescription Only
Oral
No
Parenteral
No
Topical
Yes
Sources
- WikipediaNitric oxide ↗
- NCATS31C4KY9ESH ↗
- ChEMBLCHEMBL1234579 ↗
- ChEMBLCHEMBL1200689 ↗
Also known as
- edrf
- edrf
- endothelium-derived relaxing factor
- endothelium-derived relaxing factor
- inomax
- inomax
- inomax
- inomax
- mononitrogen monoxide
- mononitrogen monoxide
- monoxido de nitrogeno
- monoxido de nitrogeno
- monoxyde d'azote
- monoxyde d'azote
- nitric oxide
- nitric oxide
- nitric oxide
- nitric oxide
- nitric oxide
- nitric oxide
- nitric oxide
- nitric oxide
- nitric oxide
- nitric oxide
- nitric oxide
- nitric oxide
- nitrogen monooxide
- nitrogen monooxide
- nitrogen monoxide
- nitrogen monoxide
- nitrogen monoxide
- nitrogen monoxide
- nitrogen monoxide
- nitrogen oxide
- nitrosyl
- nitrosyl
- no
- no
- (.)no
- (.)no
- (no)(.)
- (no)(.)
- [no]
- [no]
- no(.)
- no(.)
- oxido de nitrogeno(ii)
- oxido de nitrogeno(ii)
- oxido nitrico
- oxido nitrico
- oxyde azotique
- oxyde azotique
- oxyde nitrique
- stickstoff(ii)-oxid
- stickstoff(ii)-oxid
- stickstoffmonoxid
- stickstoffmonoxid
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT07247240 | Phase 4 | Nov 30, 2025 | Chungnam National University, Seoul National University, University of Ulsan, Yonsei University |
| NCT06950294 | Early Phase 1 (Phase 1) | Jun 30, 2025 | Harvard University |
| NCT06702553 | Phase 3 | Dec 15, 2024 | Xijing Hospital |
| NCT06636357 | Phase 2 | Nov 1, 2024 | University of Zurich |
| NCT06622291 | Phase 4 | Oct 8, 2024 | Capital Medical University |
| NCT06539013 | N/A | Aug 1, 2024 | Saglik Bilimleri Universitesi |
| NCT05871606 | Phase 1 | Apr 30, 2024 | Mallinckrodt, Wake Forest University |
| NCT06249633 | Early Phase 1 (Phase 1) | Feb 29, 2024 | Cedars-Sinai Medical Center, Mallinckrodt |
| NCT06261827 | N/A | Feb 20, 2024 | Russian Academy of Medical Sciences |
| NCT06264141 | Phase 2 | Jan 16, 2024 | Sanotize Research and Development Corp. |
| NCT06170372 | N/A | Jan 15, 2024 | Russian Academy of Medical Sciences |
| NCT06120816 | Phase 1 | Dec 31, 2023 | Sanotize Research and Development Corp. |
| NCT06213077 | N/A | Dec 12, 2023 | OnSite Clinical Solutions, RHA Investments Ltd |
| NCT06162455 | N/A | Nov 17, 2023 | Russian Academy of Medical Sciences |
| NCT06097026 | N/A | Oct 25, 2023 | Air Liquide, Universidad Autonoma de Madrid |
| NCT05616910 | Phase 2 | Aug 31, 2023 | University of Pennsylvania |
| NCT05877313 | Phase 2 | Aug 2, 2023 | Sanotize Research and Development Corp. |
| NCT05801224 | N/A | Aug 1, 2023 | Harvard University |
| NCT05896800 | N/A | Jun 1, 2023 | Nanjing Medical University |
| NCT05757557 | Phase 1/Phase 2 (Phase 2) | Feb 25, 2023 | Russian Academy of Medical Sciences |
Organizations
Research & Development (178)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| Mallinckrodt | For profit | 41 | 15 | 5 | 1998 |
| Harvard University | Academic/Hospital | 17 | 14 | 4 | 2005 |
| Bellerophon Therapeutics | For profit | 13 | 10 | 4 | 2012 |
| Sanotize Research and Development Corp. | For profit | 9 | 9 | 3 | 2019 |
| National Heart, Lung, and Blood Institute (NHLBI) | Government | 7 | 3 | 3 | 2000 |
| Russian Academy of Medical Sciences | Academic/Hospital | 7 | 7 | 2 | 2015 |
| University of Cincinnati | Academic/Hospital | 7 | 3 | 1 | 1995 |
| National Institutes of Health (NIH) | Government | 6 | 3 | 3 | 1992 |
| Nitric BioTherapeutics, Inc | For profit | 6 | 5 | 1 | 2005 |
| University of Alabama, Birmingham | Academic/Hospital | 6 | 2 | 3 | 1998 |
| Xijing Hospital | Academic/Hospital | 6 | 5 | 2 | 2013 |
| Indiana University | Academic/Hospital | 5 | 1 | 2 | 1995 |
| Advanced Inhalation Therapies Ltd | For profit | 4 | 4 | 2 | 2013 |
| Baylor University | Academic/Hospital | 4 | 2 | 2 | 1995 |
| Novan, Inc. | For profit | 4 | 4 | 3 | 2017 |
| Stanford University | Academic/Hospital | 4 | 1 | 2 | 1995 |
| University of Alberta | Academic/Hospital | 4 | 4 | 1 | 2018 |
| University of Texas at Houston | Academic/Hospital | 4 | 1 | 2 | 1998 |
| A.O. Ospedale Maggiore di Lodi | Academic/Hospital | 3 | 0 | 1 | 2020 |
| Beyond Air Ltd | For profit | 3 | 3 | 2 | 2019 |
Marketing (11)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| AIRGAS THERAP | For profit | MKTG | Jul 27, 2023 |
| BOC International | For profit | MKTG | Oct 2, 2018 |
| INO Therapeutics | For profit | NDA | Dec 23, 1999 |
| International Minerals and Chemical Corporation | For profit | NDA2 | Dec 23, 1999 |
| Linde AG | For profit | MKTG | Oct 2, 2018 |
| Mallinckrodt | For profit | NDA2 | Dec 23, 1999 |
| Mallinckrodt | For profit | MKTG | Dec 23, 1999 |
| Praxair | For profit | MKTG | Oct 2, 2018 |
| Vero Biotech | For profit | MKTG | Dec 20, 2019 |
| Vero Biotech | For profit | SYN | Dec 20, 2019 |
| Vero Biotech | For profit | NDA2 | Dec 20, 2019 |