Therapeutic potential of nitrate esters of commonly used drugs

Current Topics in Medicinal Chemistry

Volumn 5, Issue 7, 2005, Pages 707-720

  Bolla, Manlio ^a   Almirante, Nicoletta ^b   Benedini, Francesca ^b  

^a NicOx SA   (France)

^b Nicox Research Institute   (Italy)

Author keywords

Antihypertensive drugs; Aspirin; COX inhibiting nitric oxide donators (CINODs); Gabapentin; Hybrid nitrates; Naproxen; Nitric oxide; NO donors; Non steroidal anti inflammatory drugs (NSAIDs); Steroids

Indexed keywords

1 [2 METHYL 3 [[[4 (NITROOXY)BUTOXY]CARBONYL]THIO] 1 OXOPROPYL]PROLINE; 1 [[[4 (NITROOXY)METHYL]BENZOYL]AMINO]METHYL]CYCLOHEXANEACETIC ACID; 1 [[[[4 (NITROOXY)BUTOXY]CARBONYL]AMINO]METHYL]CYCLOHEXANEACETIC ACID; 11,17 DIHYDROXY 21 [[4 [(NITROOXY)METHYL]BENZOYL]OXY]PREGNA 1,4 DIENE 3,20 DIONE; 4 (NITROOXY)BUTANOIC ACID 4 ACETYLAMINOPHENYL ESTER; ACETYLSALICYLIC ACID; ACETYLSALICYLIC ACID 3 (NITROXYMETHYL)PHENYL ESTER; ALACEPRIL; CAPTOPRIL; CYCLOOXYGENASE 2 INHIBITOR; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENALAPRIL; FENTANYL; GABAPENTIN; GLYCERYL TRINITRATE; NAPROXEN; NCX 1015; NCX 701; NCX 8006; NCX 8008; NCX 895; NITRIC ACID DERIVATIVE; NITRIC OXIDE DONOR; NITRONAPROXEN; NITROPRUSSIDE SODIUM; NONSTEROID ANTIINFLAMMATORY AGENT; PARACETAMOL; PREDNISOLONE; ROFECOXIB; STEROID; UNCLASSIFIED DRUG;

ANALGESIA; ANTIINFLAMMATORY ACTIVITY; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; DISEASE MODEL; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TOLERABILITY; ENTERITIS; GASTROINTESTINAL SYMPTOM; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; NONHUMAN; OSTEOARTHRITIS; PAIN; PERIPHERAL OCCLUSIVE ARTERY DISEASE; REVIEW; VASODILATATION;

ANGINA PECTORIS; ANIMALS; ESTERS; HUMANS; NITRATES; NITRIC OXIDE; NITRIC OXIDE DONORS;

EID: 23844459602     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/1568026054679335     Document Type: Review

References (104)

1. Ignarro, L.J.; Buga, G.M.; Wood, K.S.; Byrns, R.E.; Chaudhuri, G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc. Natl. Acad. Sci. USA 1987, 84, 9265-9269.
2. Moncada, S.; Palmer, R.M.J.; Higgs, C.A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 1991, 43, 109-142.
3. Moncada, S.; Higgs, A.; Furchgott, R. International Union of Pharmacology Nomenclature in Nitric Oxide Research. Pharmacol. Rev. 1997, 49, 137-142.
4. Brunori, M.; Giuffre, A.; Sarti, P., Stubauer, G.; Wilson, M.T. Nitric oxide and cellular respiration. Cell. Mol. Life Sci. 1999, 56, 549-557.
5. Colasanti, M.; Persichini, T. Nitric oxide: an inhibitor of NF-kB/Rel system in glyal cells. Brain Res. Bull. 2000, 52, 155-161.
6. Thatcher, G.R.; Nicolescu, A.C.; Bennett, B.M.; Toader, V. Nitrates and NO release: contemporary aspects in biological and medicinal chemistry. Free Radic. Biol. Med. 2004, 37(8), 1122-1143.
7. Keeble, J.E.; Moore, P.K. Pharmacology and potential therapeutic applications of nitric oxide-releasing non-steroidal anti-inflammatory and related nitric oxide-donating drugs. Br. J. Pharmacol. 2002, 137, 295-310.
8. Burgaud, J.L.; Ongini, E.; Del Soldato P. Nitric oxide-releasing drugs: a novel class of effective and safe therapeutic agents. Ann. N. Y. Acad. Sci. 2002, 962, 360-371.
9. Burgaud, J.L.; Riffaud J.P.; Del Soldato P. Nitric-oxide releasing molecules: a new class of drugs with several major indications. Curr. Pharm. Des. 2002, 8(3), 201-213.
10. Wolfe, M.M.; Lichtenstein, D.R.; Singh, G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N. Engl. J. Med. 1999, 340, 1888-1899.
11. Fiorucci, S.; Antonelli, E.; Burgaud, J.L.; Morelli, A. Nitric oxide-releasing NSAIDs: A review of their current status. Drug Saf. 2001, 24, 801-811.
12. Wallace, J.L.; Del Soldato P. The therapeutic potential of NONSAIDs. Fundam. Clin. Pharmacol. 2003; 17, 11-20.
13. Cirino, G. Nitric oxide releasing drugs: from bench to bedside. Dig. Liver Dis. 2003; 35 (Suppl 2), S2-8.
14. Monck, N. NO-naproxen (AstraZeneca). IDrugs 2003, 6, 593-599.
15. Hoogstraate, J.; Andersson, L.I.; Berge, O.G.; Jonzon, B.; Ojteg, G. COX-inhibiting nitric oxide donators (CINODs) - a new paradigm in the treatment of pain and inflammation. Inflammopharmacol. 2003, 11, 423-428.
16. Cirino, G.; Calignano, A.; Iannaro, A.; Cicala, C.; Del Soldato, P.; Fiorucci, S.; Wallace, J.L. NO-naproxen modulates inflammation, pain and T cell responses in rat Freund's adjuvant arthritis. Mediators Inflamm. 1999, Suppl 1, S27-S24.
17. Cicala, C.; Ianaro, A.; Fiorucci, S.; Calignano, A.; Bucci, M.; Gerli, R.; Santucci, L.; Wallace, J.L.; Cirino, G. NO-naproxen modulates inflammation, nociception and downregulates T cell response in rat Freund's adjuvant arthritis. Br. J. Pharmacol. 2000, 130, 1399-1405.
18. Cuzzolin, L.; Conforti, A.; Adami, A.; Lussignoli, S.; Menestrina, F.; Del Soldato, P.; Benoni, G. Anti-inflammatory potency and gastrointestinal toxicity of a new compound, nitronaproxen. Pharmacol. Res. 1995, 31, 61-65.
19. Brzozowski, T.; Konturek, P.C.; Konturek, S.J.; Sliwowski, Z.; Drozdowicz, D.; Kwiecien, S.; Pajdo, R.; Ptak, A,; Pawlik, M.; Hahn, E. Gastroprotective and ulcer healing effects of nitric oxide releasing non-steroidal anti-inflammatory drugs. Dig. Liver Dis. 2000, 32, 583-594.
20. Davies, N.M.; Roseth, A.G.; Appleyard, C.B.; McKnight, W.; Del Soldato, P.; Calignano, A.; Cirino, G.; Wallace, J.L. NO-naproxen vs. naproxen: Ulcerogenic, analgesic and anti-inflammatory effects. Aliment. Pharmacol. Ther. 1997, 11, 69-79.
21. Maricic, N.; Ehrlich, K.H.; Peskar, B.M. Effect of NO-naproxen on ischemia-reperfusion damage in the rat stomach: Comparison with naproxen and selective cyclooxygenase-2 inhibitors. Am. Gastroenterol. Assoc. 1999, May 16-19, Orlando, FL, Abs 1991.
22. Fiorucci, S.; Di Lorenzo, A.; Renga, B.; Farneti, S.; Morelli, A.; Cirino, G. Nitric oxide (NO)-releasing naproxen (HCT-3012 [(S)-6-methoxy-alpha-methyl-2-naphthaleneacetic Acid 4-(nitrooxy) butyl ester]) interactions with aspirin in gastric mucosa of arthritic rats reveal a role for aspirin-triggered lipoxin, prostaglandins, and NO in gastric protection. J. Pharmacol. Exp. Ther. 2004, 311, 1264-71.
23. Fiorucci, S.; Santucci, L.; Federici, B.; Antonelli, E.; Distrutti, E.; Morelli, O.; Renzo, G.D.; Coata, G.; Cirino, G.; Del Soldato, P.; Morelli, A. Nitric oxide-releasing NSAIDs inhibit interleukin-1 converting enzyme-like cysteine proteases and protect endothelial cells from apoptosis induced by TNFα. Aliment. Pharmacol. Ther. 1999, 13, 421-435.
24. Berndt, G.; Grosser, N.; Hoogstraate, J.; Schroder, H. A common pathway of nitric oxide release from AZD3582 and glyceryl trinitrate. Eur. J. Pharm. Sci. 2004, 21, 331-335.
25. Rossoni, G.; Manfredi, B.; Del Soldato, P.; Berti, F. The nitric oxide-releasing naproxen derivative displays cardioprotection in perfused rabbit heart submitted to ischemia-reperfusion. J. Pharmacol. Exp. Ther. 2004, 310, 555-562.
26. Muscara, M.N.; McKnight, W.; Del Soldato, P.; Wallace, J.L. Effect of a nitric oxide-releasing naproxen derivative on hypertension and gastric damage induced by chronic nitric oxide inhibition in the rat. Life Sci. 1998, 62, PL235-240.
27. Muscara, M.N.; McKnight, W.; Lovren, F.; Triggle, C.R.; Cirino, G.; Wallace, J.L. Antihypertensive properties of a nitric oxide-releasing naproxen derivative in two-kidney, one-clip rats. Am. J. Physiol. Heart Circ. Physiol. 2000, 279, H528-H535.
28. Hawkey, C.J.; Jones, J.I.; Atherton, C.T.; Skelly, M.M.; Bebb, J.R.; Fagerholm, U.; Jonzon, B.; Karlsson, P.; Bjarnason, I.T. Gastrointestinal safety of AZD3582, a cyclooxygenase inhibiting nitric oxide donator: proof of concept study in humans. Gut 2003, 52, 1537-1542.
29. Jonzon, B.; Bjarnason, I.; Hawkey, C.; Jones, J.; Goddard, A.; Fagerholm, U.; Karlsson, P. The CINOD, AZD3582, exhibits an improved gastrointestinal safety profile compared with naproxen in healthy volunteers. Inflammopharmacol. 2003, 11, 437-444.
30. Lohmander, L.S.; McKeith, D.; Svensson, O.; Malmenas, M.; Bolin, L.; Kalla, A.; Genti, G.; Szechinski, J.; Ramos-Remus, C. A randomised, placebo controlled, comparative trial of the gastrointestinal safety and efficacy of AZD3582 versus naproxen in osteoarthritis. Ann. Rheum. Dis. 2005, 64, 449-456.
31. Schnitzer T, Ballabio M, Bonizzoni E. AZD3582, a CINOD, differs significantly from rofecoxib in having a neutral effect on blood pressure in patients with osteoarthritis: results of a randomized controlled trial. ACR/ARHP Annual Scientific Meeting 2004, San Antonio, TX, USA, 16-21 October, Abs#1859.
32. Vainio, H.; Morgan, G. Aspirin for the second hundred years: new uses for an old drug. Pharmacol. Toxicol. 1997, 81, 151-152.
33. Chiroli, V.; Benedini, F.; Ongini, E.; Del Soldato, P. Nitric oxide-donating non-steroidal anti-inflammatory drugs: the case of nitroderivatives of aspirin. Eur. J. Med. Chem. 2003, 38, 441-446.
34. Fiorucci, S.; Del Soldato, P. NO-aspirin: mechanism of action and gastrointestinal safety. Dig. Liver Dis. 2003, 35(S2), S9-S19.
35. Wallace, J.L.; Ignarro, L.J.; Fiorucci, S. Potential cardioprotective actions of NO-releasing aspirin. Nat. Rev. Drug Discov. 2002, 1, 375-382.
36. Boll, M.; Acuto, G.; Del Soldato, P. Nitric Oxide donating aspirins spare the gastrointestinal (GI) system and improve the treatment of inflammation-related GI and cardiovascular pathologies. In Pharmacotherapy of Gastrointestinal Inflammation; Guglietta, A.; Ed.; Birkhauser Verlag: Basel CH, 2004; pp. 93-108.
37. Di Napoli, M.; Papa, F. NCX-4016 NicOx. Curr. Opin. Investig. Drugs 2003, 4, 1126-1139.
38. Fiorucci, S.; Santucci, L.; Cirino, G.; Mencarelli, A.; Familiari, L.; Soldato, P.D.; Morelli, A. IL-1 beta converting enzyme is a target for nitric oxide-releasing aspirin: new insights in the antiinflammatory mechanism of nitric oxide-releasing nonsteroidal antiinflammatory drugs. J. Immunol. 2000, 165, 5245-5254.
39. Takeuchi, K.; Ukawa, H.; Konaka, A.; Kitamura, M.; Sugawa, Y. Effect of nitric oxide-releasing aspirin derivative on gastric functional and ulcerogenic responses in rats: comparison with plain aspirin. J. Pharmacol. Exp. Ther. 1998, 286, 115-121.
40. Wallace, J.L.; McKnight, W.; Wilson, T.L.; Del Soldato, P.; Cirino, G. Reduction of shock-induced gastric damage by a nitric oxide-releasing aspirin derivative: role of neutrophils. Am. J. Physiol. Gastrointest. Liver Physiol. 1997, 273, G1246-G1251.
41. Kato, S.; Suzuki, K.; Ukawa, H.; Komoike, Y.; Takeuchi, K. Low gastric toxicity of nitric oxide-releasing aspirin, NCX-4016, in rats with cirrhosis and arthritis. Dig. Dis. Sci. 2001, 46, 1690-1699.
42. Tashima, K.; Fujita, A.; Umeda, M.; Takeuchi, K. Lack of gastric toxicity of nitric oxide-releasing aspirin, NCX-4016, in the stomach of diabetic rats. Life Sci. 2000, 67, 1639-1652.
43. Fiorucci, S.; Santucci, L.; Wallace, J.L.; Sardina, M.; Romano, M.; Del Soldato, P.; Morelli, A. Interaction of a selective cyclooxygenase-2 inhibitor with aspirin and NO-releasing aspirin in the human gastric mucosa. Proc. Natl. Acad. Sci. USA 2003, 100, 10937-10941.
44. Fiorucci, S.; Santucci, L.; Gresele, P.; Facino, R.M.; Del Soldato, P.; Morelli, A. Gastrointestinal safety of NO-aspirin (NCX-4016) in healthy human volunteers: a proof of concept endoscopic study. Gastroenterology 2003, 124, 600-607.
45. Fiorucci, S.; Mencarelli, A.; Meneguzzi, A.; Lechi, A.; Renga, B.; Del Soldato, P.; Morelli, A.; Minuz, P. Co-administration of nitric oxide-aspirin (NCX-4016) and aspirin prevents platelet and monocyte activation and protects against gastric damage induced by aspirin in humans. J. Am. Coll. Cardiol. 2004, 44, 635-641.
46. Wallace, J.L.; Zamuner, S.R.; McKnight, W.; Dicay, M.; Mencarelli, A.; Del Soldato, P.; Fiorucci, S. Aspirin, but not NO-releasing aspirin (NCX-4016), interacts with selective COX-2 inhibitors to aggravate gastric damage and inflammation. Am J Physiol Gastrointest Liver Physiol. 2004, 286, G76-G81.
47. Corazzi, T.; Leone, M.; Roberti, R.; Del Soldato, P.; Gresele, P. Effect of nitric oxide-donating agents on human monocyte cyclooxygenase-Biochem. Biophys. Res. Commun. 2003, 311, 897-903.
48. Minuz, P.; Degan, M.; Gaino, S.; Meneguzzi, A.; Zuliani, V.; Santonastaso, C. L.; Soldato P. D.; Lechi, A. NCX4016 (NO-Aspirin) has multiple inhibitory effects in LPS-stimulated human monocytes. Br. J. Pharmacol. 2001, 134, 905-911.
49. Minuz, P.; Degan, M.; Gaino, S.; Meneguzzi, A.; Zuliani, V.; Lechi Santonastaso, C.; Del Soldato, P., Lechi, A. NCX4016 (NO-aspirin) inhibits thromboxane biosynthesis and tissue factor expression and activity in human monocytes. Med. Sci. Monit. 2001, 7, 573-77.
50. al-Swayeh, O. A.; Clifford, R. H.; del Soldato, P.; Moore, P. K. A comparison of the anti-inflammatory and anti-nociceptive activity of nitroaspirin and aspirin. Br. J. Pharmacol. 2000, 129, 343-350.
51. Fiorucci, S.; Distrutti, E.; Mencarelli, A.; Rizzo, G.; Lorenzo, A. R.; Baldoni, M.; Del Soldato, P.; Morelli, A.; Wallace, J. L. Cooperation between Aspirin-Triggered Lipoxin and Nitric Oxide (NO) Mediates Antiadhesive Properties of 2-(Acetyloxy)benzoic Acid 3-(Nitrooxymethyl)phenyl Ester (NCX-4016) (NO-Aspirin) on Neutrophil-Endothelial Cell Adherence. J. Pharmacol. Exp. Ther. 2004, 309, 1174-82.
52. Rossoni, G.; Manfredi, B.; Colonna, V. D.; Bernareggi, M.; Berti, F. The nitroderivative of aspirin, NCX 4016, reduces infarct size caused by myocardial ischemia-reperfusion in the anesthetized rat J. Pharmacol. Exp. Ther. 2001, 297, 380-387.
53. Rossoni, G.; Muscara, M. N.; Cirino, G.; Wallace, J. L. Inhibition of cyclo-oxygenase-2 exacerbates ischaemia-induced acute myocardial dysfunction in the rabbit. Br. J. Pharmacol. 2002, 135, 1540-1546.
54. Wainwright, C. L.; Miller, A. M.; Work, L. M.; Del Soldato, P. NCX4016 (NO-aspirin) reduces infarct size and suppresses arrhythmias following myocardial ischaemia/reperfusion in pigs. Br. J. Pharmacol. 2002, 135, 1882-1888.
55. Napoli, C.; Cirino, G.; Del Soldato, P.; Sorrentino, R.; Sica, V.; Condorelli, M.; Pinto, A.; Ignarro, L. J. Effects of nitric oxide-releasing aspirin versus aspirin on restenosis in hypercholesterolemic mice. Proc. Natl. Acad. Sci. USA 2001, 98, 2860-2864.
56. Napoli, C.; Ackah, E.; De Nigris, F.; Del Soldato, P.; D'Armiento, F.P.; Crimi, E.; Condorelli, M.; Sessa, W. C. Chronic treatment with nitric oxide-releasing aspirin reduces plasma low-density lipoprotein oxidation and oxidative stress, arterial oxidation-specific epitopes, and atherogenesis in hypercholesterolemic mice. Proc. Natl. Acad. Sci. USA 2002, 99, 12467-12470.
57. Napoli, C.; Aldini, G.; Wallace, J. L.; de Nigris, F.; Maffei, R.; Abete, P.; Bonaduce, D.; Condorelli, G.; Rengo, F.; Sica, V.; D'Armiento, F. P.; Mignogna, C.; de Rosa, G.; Condorelli, M.; Lerman, L. O.; Ignarro, L. J. Efficacy and age-related effects of nitric oxide-releasing aspirin on experimental restenosis. Proc. Natl. Acad. Sci. USA 2002, 99, 1689-1694.
58. Momi, S.; Emerson, M.; Paul, W.; Leone, M.; Mezzasoma, A. M.; Del Soldato, P.; Page, C. P.; Gresele, P. Prevention of pulmonary thromboembolism by NCX 4016, a nitric oxide-releasing aspirin. Eur. J. Pharmacol. 2000, 397, 177-185.
59. Momi, S.; Leone, M.; Mezzasoma, A. M.; Del Soldato, P.; Gresele, P. NCX4016, an aspirin (ASA) derivative releasing nitric oxide (NO), prevents pulmonary thromboembolism in mice more extensively than ASA. Thromb. Haemost. 1999, 81(Suppl), 265.
60. Momi, S.; Pitchford, S.; Alberti, P. F.; Minuz, P.; Del Soldato, P.; Gresele, P. Nitroaspirin plus clopidogrel versus aspirin plus clopidogrel against platelet thromboembolism and intimal thickening in mice. Thromb. Haemost. 2005, 93, 535-543.
61. Gresele, P.; Migliacci, R.; Bonizzoni, E.; Sardina, M. Nitroaspirin prevents effort-induced endothelial dysfunction in intermittent claudication. Circulation 2004, SIII 110 (17), 520. 62 Joshi, G. P. NCX-NicOx. Curr. Opin. Investig. Drugs 2004, 5, 755-759.
62. Joshi, G. P. NCX-NicOx. Curr. Opin. Investig. Drugs 2004, 5, 755-759.
63. Moore, P. K.; Marshall, M. Nitric oxide releasing acetaminophen (nitroacetaminophen). Dig. Liver Dis. 2003, 35(S2), S49-S60.
64. Fiorucci, S.; Antonelli, E.; Mencarelli, A.; Palazzetti, B.; Alvarez-Miller, L.; Muscara, M.; del Soldato, P.; Sanpaolo, L.; Wallace, J.L.; Morelli, A. A NO-releasing derivative of acetaminophen spares the liver by acting at several checkpoints in the Fas pathway. Br. J. Pharmacol. 2002, 135, 589-599.
65. Futter, L. E.; al-Swayeh, O. A.; Moore, P. K. A comparison of the effect of nitroparacetamol and paracetamol on liver injury. Br. J. Pharmacol. 2001, 132, 10-12.
66. Wallace, J. L. Acetaminophen hepatotoxicity: NO to the rescue. Br. J. Pharmacol. 2004, 143, 1-2.
67. Marshall, M.; Moore, P. K. Effect of nitric oxide releasing paracetamol and flurbiprofen on cytokine production in human blood. Eur. J. Pharmacol. 2004, 483, 317-322.
68. al-Swayeh, O. A.; Futter, L. E.; Clifford, R. H.; Moore, P. K. Nitroparacetamol exhibits anti-inflammatory and anti-nociceptive activity. Br. J. Pharmacol. 2000, 130, 1453-1456.
69. Paul Clark, M. J.; Howat, D.; Flower, R. J.; Moore, P. K.; Perretti, M. Nitroparacetamol (NCX-701) exhibits anti-inflammatory activity in the zymosan air pouch. Inflamm. Res. 2001, 50, S158.
70. Romero-Sandoval, E. A.; Mazario, J.; Howat, D.; Herrero, J. F. NCX-701 (nitroparacetamol) is an effective antinociceptive agent in rat withdrawal reflexes and wind-up. Br. J. Pharmacol. 2002, 135, 1556-62.
71. Romero-Sandoval A. E.; Del Soldato, P.; Herrero, J. F. The effects of sham and full spinalization on the antinociceptive effects of NCX-701 (nitroparacetamol) in monoarthritic rats. Neuropharmacology 2003, 45, 412-9.
72. Gaitan, G.; Del Soldato, P.; Herrero, J. F. Low doses of nitroparacetamol or dexketoprofen trometamol enhance fentanyl antinociceptive activity. Eur. J. Pharmacol. 2003, 481, 181-188.
73. Olson, N. Z.; Sunshine, A.; Otero, A.; Tirado, S.; Ballabio, M.; Sardina, M. Analgesic efficacy of a new NO-derivative of acetaminophen (NCX 701) in post-surgical dental pain: A Preliminary Report. 6th World Congress on Inflammation, Vancouver, CAN August. 2003, Abs #L11.5.
74. Perretti, M.; Paul-Clark, M. J.; Mancini, L.; Flower, R. J. Generation of innovative anti-inflammatory and anti-arthritic glucocorticoid derivatives that release NO: the nitro-steroids. Dig. Liver Dis. 2003, 35(S2), S41-S48.
75. Tallet, D.; Del Soldato, P.; Oudart, N.; Burgaud, J.L. NO-steroids: potent anti-inflammatory drugs with bronchodilating activity in vitro. Biochem. Biophys. Res. Commun. 2002, 290, 125-130.
76. Hyun, E.; Bolla, M.; Steinhoff, M.; Wallace, J. L.; Soldato, P. D.; Vergnolle, N. Anti-inflammatory effects of nitric oxide-releasing hydrocortisone NCX 1022, in a murine model of contact dermatitis. Br. J. Pharmacol. 2004, 143, 618-25.
77. Baraldi, P. G.; Romagnoli, R.; Del Carmen Nunez, M.; Perretti, M.; Paul-Clark, M. J.; Ferrario, M.; Govoni, M.; Benedini, F.; Ongini, E. Synthesis of nitro esters of prednisolone, new compounds combining pharmacological properties of both glucocorticoids and nitric oxide. J. Med. Chem. 2004, 47, 711-719.
78. Paul-Clark, M.; Del Soldato, P.; Fiorucci, S.; Flower, R. J.; Perretti, M. 21-NO-prednisolone is a novel nitric oxide-releasing derivative of prednisolone with enhanced anti-inflammatory properties. Br. J. Pharmacol. 2000, 131, 1345-1354.
79. Paul-Clark, M. J.; Mancini, L.; Del Soldato, P.; Flower, R. J.; Perretti, M. Potent antiarthritic properties of a glucocorticoid derivative, NCX-1015, in an experimental model of arthritis. Proc. Natl. Acad. Sci. USA 2002, 99, 1677-1682.
80. Turesin, F.; del Soldato, P.; Wallace, J. L. Enhanced anti-inflammatory potency of a nitric oxide-releasing prednisolone derivative in the rat. Br. J. Pharmacol. 2003, 139, 966-72.
81. Wallace, J. L.; Rizzo, G.; Cirino, G.; Del Soldato, P.; Fiorucci, S. Enhanced anti-inflammatory potency of a nitric oxide-releasing derivative of flunisolide: role of nuclear factor-kappaB. J. Pharmacol. Exp. Ther. 2004, 310, 1096-1102.
82. Paul-Clark, M. J.; Roviezzo, F.; Flower, R. J.; Cirino, G.; Soldato, P. D.; Adcock, I. M.; Perretti, M. Glucocorticoid receptor nitration leads to enhanced anti-inflammatory effects of novel steroid ligands. J. Immunol. 2003, 171, 3245-3252.
83. Paul-Clark, M. J.; Perretti, M. The enhanced anti-inflammatory properties of nitro-prednisolone (NCX 1015) is linked to post-translational modification of the glucocorticoid receptor. Inflamm. Res. 2003, 52(S2), 96-98.
84. Fiorucci, S.; Antonelli, E.; Distrutti, E.; Del Soldato, P.; Flower, R. J.; Clark, M. J.; Morelli, A.; Perretti, M.; Ignarro, L. J. NCX-1015, a nitric-oxide derivative of prednisolone, enhances regulatory T cells in the lamina propria and protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice. Proc. Natl. Acad. Sci. USA 2002, 99, 15770-15775.
85. Keeble, J.; al-Swayeh, O.A.; Moore, P. K. Vasorelaxant effect of nitric oxide releasing steroidal and non steroidal anti-inflammatory drugs. Br. J. Pharmacol. 2001, 133, 1023-1028.
86. Di Filippo, C.; Rossi, F.; Ongini, E.; Del Soldato, P.; Perretti, M.; D'Amico, M. The distinct alterations produced in cardiovascular functions by prednisolone and nitro-prednisolone (NCX-1015) in the rat highlight a causal role for endothelin-J. Pharmacol. Exp. Ther. 2004, 310, 1133-1141.
87. Peskar, B. M.; Maricic, N.; Ehrlich, K.; Sawka, N. NCX-1015, a Novel Nitric Oxide-Releasing Derivative of Prednisolone, Combines Potent Anti-Inflammatory Activity and Low Toxicity in the Rat Stomach Subjected to Ischemia-Reperfusion. Gastroenterology 2002, 122, A-229-230, M891.
88. Cardillo, C.; Kilcoyne, C. M.; Quyyumi, A. A.; Cannon, R.O. 3rd.; Panza, J. A. Selective defect in nitric oxide synthesis may explain the impaired endothelium-dependent vasodilation in patients with essential hypertension. Circulation 1998, 97, 851-856.
89. Loscalzo, J.; Smick, D.; Andon, N.; Cooke, J. S-nitrosocaptopril. I. Molecular characterization and effects on the vasculature and on platelets. J. Pharmacol. Exp. Ther. 1989, 249, 726-729.
90. Cooke, J. P.; Andon, N.; Loscalzo, J. S-nitrosocaptopril. II. Effects on vascular reactivity. J. Pharmacol. Exp. Ther. 1989, 249, 730-734.
91. Jia, L.; Pei, R.; Lin, M.; Yang, X. Acute and subacute toxicity and efficacy of S-nitrosylated captopril, an ACE inhibitor possessing nitric oxide activities. Food Chem. Toxicol. 2001, 39, 1135-1143.
92. Iwanaga, Y.; Gu, Y.; Dieterle, T.; Presotto, C.; Del Soldato, P.; Peterson, K. L.; Ongini, E.; Condorelli, G.; Ross, J. Jr. A nitric oxide-releasing derivative of enalapril, NCX 899, prevents progressive cardiac dysfunction and remodeling in hamsters with heart failure. FASEB J. 2004, 18, 587-588.
93. Wu, W. -P.; Hao, J. -X; Ongini, E.; Impagnatiello, F.; Presotto, C.; Wiesenfeld-Hallin, Z.; Xu, X. -J. A nitric oxide (NO)-releasing derivative of gabapentin, NCX 8001, alleviates neuropathic pain-like behavior after spinal cord and peripheral nerve injury). Br. J. Pharmacol. 2004, 141, 65-74.
94. Aldini, G.; Carini, M.; Orioli, M.; Facino, R. M.; Wenk, G. L. Metabolic profile of NO-flurbiprofen (HCT1026) in rat brain and plasma: a LC-MS study. Life Sci. 2002, 71, 1487-500.
95. Carini, M.; Aldini, G.; Orioli, M.; Piccoli, A.; Tocchetti, P.; Facino, R. M. Chemiluminescence and LC-MS/MS analyses for the study of nitric oxide release and distribution following oral administration of nitroaspirin (NCX 4016) in healthy volunteers. J. Pharm. Biomed. Anal. 2004, 35, 277-287.
96. Carini, M.; Aldini, G.; Orioli, M.; Piccoli, A.; Rossoni, G.; Maffei Facino, R. Nitric oxide release and distribution following oral and intraperitoneal administration of nitroaspirin (NCX 4016) in the rat. Life Sci. 2004, 74, 3291-3305.
97. Gasco, A.; Fruttero, R.; Rolando, B. Focus on recent approaches for the development of new NO-donors. Mini Rev. Med. Chem. 2005, 5, 217-229.
98. Grosser, N.; Schroder, H. A common pathway for nitric oxide release from NO-aspirin and glyceryl trinitrate. Biochem. Biophys. Res. Commun. 2000, 274, 255-258.
99. Berndt, G.; Grosser, N.; Hoogstraate, J.; Schroder, H. A common pathway of nitric oxide release from AZD3582 and glyceryl trinitrate. Eur. J. Pharm. Sci. 2004, 21, 331-335.
100. Schröder, H. Cytochrome P-450 mediates bioactivation of organic nitrates. J. Pharmacol. Exp. Ther. 1992, 262, 298-302
101. Gao, J.; Kashfi, K.; Rigas, B. In vitro metabolism of nitric oxide-donating aspirin: the effect of positional isomerism. J. Pharmacol. Exp. Ther. 2005, 312, 989-997.
102. Kashfi, K.; Borgo, S.; Williams, J. L.; Chen, J.; Gao, J.; Glekas, A.; Benedini, F.; Del Soldato, P.; Rigas, B. Positional isomerism markedly affects the growth inhibition of colon cancer cells by nitric oxide-donating aspirin in vitro and in vivo. J. Pharmacol. Exp. Ther. 2005, 312, 978-988.
103. Carini, M.; Aldini, G.; Stefani, R.; Orioli, M.; Facino, R. M. Nitrosylhemoglobin, an unequivocal index of nitric oxide release from nitroaspirin: in vitro and in vivo studies in the rat by ESR spectroscopy. J. Pharm. Biomed. Anal. 2001, 26, 509-518.
104. Carini, M.; Aldini, G.; Orioli, M.; Maffei Facino, R. In vitro metabolism of a nitroderivative of acetylsalicylic acid (NCX4016) by rat liver: LC and LC-MS studies. J. Pharm. Biomed. Anal. 2002, 29, 1061-1071.