Table 1.
Major classes of NO donors and their examples of their proposed clinical uses.
| Class | Mechanism of Action [207,208] | Examples [207] | Known or Potential Clinical Uses |
|---|---|---|---|
| Endogenous NO precursors | Provide excess reagents or intermediates for NO synthesis. Direct antioxidant. Reversal of NOS inhibition. | L-Arginine, ω-hydroxy-L-arginine (NHA) | Stroke [209], Pulmonary hypetesion [210] |
| Organic Nitrates | Stimulation of guanylyl cyclase pathway, through unknown intermediate. May activate enzymatic NO production through cytochrome P450 or glutathione-S-transferase. Non-enzymatic thiol activity also described, although reaction proceeds at slower rate | Glyceryl trinitrate (GTN), isosorbide mononitrate (ISMN), pentaerythritol tetranitrate (PETN). nicorandil | Cardiac Angina [211], acute coronary syndrome [212], heart failure [213] |
| Organic Nitrites | Activation of NO signaling pathways | Butyl nitrite (BN), isobutyl nitrite (ISBN), tert-butyl nitrite (TBN), amyl nitrite (AMN), isoamyl nitrite (IAMN) | Minimal clinical uses due to cardiotoxicity and cytotoxicity |
| Metal Complexes | Direct release of NO. NO bound to metals such as iron is prone to nucleophilic attack | Sodium Nitroprusside (SNP) | Hypertensive Emergency, cardiac and aortic surgery [214,215], heart failure [216], acute coronary syndrome [217], pheochromocytoma [218] |
| Diazeniumdiolates | Spontaneously decompress to 2 molecules of NO | Methylamine hexa-methylene methylamine NONOate (MAHMA/NO), diethylamine NONOate (DEA/NO), proli NONOate (PROLI/NO) and diethylenetriamine NONOate (DETA/NO) | No current clinical uses |
| Sydnonimines | Spontaneous enzymatic degradation to O2 and NO. Also known as ONOO-donors. cGMP independent activation. Increase in K+ channel activity | 3-morpholinosydnonimine (SIN-1), molsidomine (N-ethoxycarbonyl-3-morpholinosydnonimine) | Minimal clinical trial evidence to support use [207] |
| S-nitrosothiols | Cleavage of S-NO bond releases NO and disulfide. S-nitrosation of cellular components. cGMP stimulation. |
S-nitrosoglutathione (GSNO), N-acetylpenicill-amine (SNAP), trityl S-nitrosothiol, (Ph3SNO) and tert-butyl S-nitrosothiol (tButSNO) | Onychomycosis [207], sexual dysfunction [219], antiplatelet agent [220], cardiac surgery [221], cystic fibrosis [222] |