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  1. Article: Selective nitros(yl)ation induced in vivo by a nitric oxide-donating cyclooxygenase-2 inhibitor: a NObonomic analysis.

    Dhawan, Vijay / Schwalb, David J / Shumway, Matthew J / Warren, Michael C / Wexler, Roseanne S / Zemtseva, Irina S / Zifcak, Brian M / Janero, David R

    Free radical biology & medicine

    2005  Volume 39, Issue 9, Page(s) 1191–1207

    Abstract: Nitric oxide (NO) enhances anti-inflammatory drug action. Through a metabonomics approach termed "NObonomics," the effects of a prototypic NO donor (organic nitrate)-cyclooxygenase-2 inhibitor hybrid (NO-coxib), NMI-1093, on the NO metabolite status of ... ...

    Abstract Nitric oxide (NO) enhances anti-inflammatory drug action. Through a metabonomics approach termed "NObonomics," the effects of a prototypic NO donor (organic nitrate)-cyclooxygenase-2 inhibitor hybrid (NO-coxib), NMI-1093, on the NO metabolite status of the circulation and major organs have been profiled in vivo in the rat. An oral anti-inflammatory NMI-1093 bolus elicited acute tissue-, time-, and dose-dependent changes in oxidative and nitroso/nitrosyl NO metabolites. Gastric N-nitrosation and hepatic S-nitrosation and heme nitrosylation emerged as sensitive indices of this NO-coxib's metabolism. Acute NMI-1093-induced nitros(yl)ation correlated positively as a function of nitrate plus nitrite formation across all organs examined, suggesting a unifying in vivo mechanism consequent to NMI-1093 biotransformation that links oxidative and nitros(yl)ative routes of NO chemical biology and thereby may support downstream NO signaling. NMI-1093 depressed erythrocyte nitros(yl)ation, likely by inhibiting cellular carbonic anhydrase and shifting the intracellular balance between nitrogen oxides and carbonates. Glutathione-S-transferase or cytochrome P450 inhibitors also attenuated NMI-1093's NO metabolism in a compartment-selective fashion. Although not itself a NO donor, the des-nitro coxib analog of NMI-1093 influenced basal NO metabolite profiles, implicating a cyclooxygenase-NO synthase interaction in physiological NO regulation. By detailing the global NO metrics of a unique coxib bearing a popular NO-donor pharmacophore (i.e., a nitrate moiety) and defining some critical mechanistic determinants, this study demonstrates how NObonomics can serve as valuable tool in helping elucidate NO systems biology and the effect of NO-donor and non-NO-donating therapeutics thereon.
    MeSH term(s) Animals ; Brain/drug effects ; Brain/metabolism ; Carbonic Anhydrases/drug effects ; Cyclooxygenase 2 Inhibitors/administration & dosage ; Cyclooxygenase 2 Inhibitors/chemistry ; Cyclooxygenase 2 Inhibitors/pharmacology ; Dose-Response Relationship, Drug ; Erythrocytes/enzymology ; Heme/metabolism ; Kidney/drug effects ; Kidney/metabolism ; Liver/drug effects ; Liver/metabolism ; Male ; Nitrates/metabolism ; Nitric Oxide/metabolism ; Nitric Oxide Donors/administration & dosage ; Nitric Oxide Donors/chemistry ; Nitric Oxide Donors/pharmacology ; Nitrites/metabolism ; Oxazoles/administration & dosage ; Oxazoles/chemistry ; Oxazoles/pharmacology ; Oxidation-Reduction ; Rats ; Rats, Sprague-Dawley ; Stomach/drug effects ; Stomach/metabolism ; Sulfonamides/administration & dosage ; Sulfonamides/chemistry ; Sulfonamides/pharmacology
    Chemical Substances Cyclooxygenase 2 Inhibitors ; NMI-1093 ; Nitrates ; Nitric Oxide Donors ; Nitrites ; OH-valdecoxib ; Oxazoles ; Sulfonamides ; Nitric Oxide (31C4KY9ESH) ; Heme (42VZT0U6YR) ; Carbonic Anhydrases (EC 4.2.1.1)
    Language English
    Publishing date 2005-11-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 807032-5
    ISSN 1873-4596 ; 0891-5849
    ISSN (online) 1873-4596
    ISSN 0891-5849
    DOI 10.1016/j.freeradbiomed.2005.06.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Synthesis and anti-inflammatory activity of a series of N-substituted naproxen glycolamides: nitric oxide-donor naproxen prodrugs.

    Ranatunge, Ramani R / Augustyniak, Michael E / Dhawan, Vijay / Ellis, James L / Garvey, David S / Janero, David R / Letts, L Gordon / Richardson, Stewart K / Shumway, Mathew J / Trocha, A Mark / Young, Delano V / Zemtseva, Irina S

    Bioorganic & medicinal chemistry

    2006  Volume 14, Issue 8, Page(s) 2589–2599

    Abstract: A series of glycolamide naproxen prodrugs containing a nitrate group as a nitric oxide (NO) donor moiety has been synthesized. These compounds were evaluated for their anti-inflammatory activity, naproxen release, and gastric tolerance. Compounds 4a, 4b, ...

    Abstract A series of glycolamide naproxen prodrugs containing a nitrate group as a nitric oxide (NO) donor moiety has been synthesized. These compounds were evaluated for their anti-inflammatory activity, naproxen release, and gastric tolerance. Compounds 4a, 4b, 5a, 5b, 7b, and 7c exhibited anti-inflammatory activity equivalent to that of the parent NSAID, naproxen-Na, in the rat carrageenan paw edema model. At equimolar doses relative to naproxen-Na, the NO-donor glycolamide derivatives 4a, 4b, 5a, 5b, 7b, and 7c were gastro-sparing in the rat. Naproxen formation from these NO-donor glycolamides varied among the structures examined, with the N-substituent on the amide group having a particular influence, and demonstrated their prodrug nature. Compound 7b was selected for exemplary demonstration that the glycolamide nitrates can be bioactivated to release NO. These data open the possibility that naproxen glycolamide nitrates may represent a safer alternative to naproxen as anti-inflammatory medicines.
    MeSH term(s) Amides/chemistry ; Animals ; Anti-Inflammatory Agents/chemical synthesis ; Anti-Inflammatory Agents/chemistry ; Anti-Inflammatory Agents/pharmacology ; Gastritis/chemically induced ; Humans ; Magnetic Resonance Spectroscopy ; Male ; Mass Spectrometry ; Naproxen/chemical synthesis ; Naproxen/chemistry ; Naproxen/pharmacology ; Nitric Oxide Donors/chemical synthesis ; Nitric Oxide Donors/chemistry ; Nitric Oxide Donors/pharmacology ; Prodrugs ; Rats ; Rats, Sprague-Dawley
    Chemical Substances Amides ; Anti-Inflammatory Agents ; Nitric Oxide Donors ; Prodrugs ; Naproxen (57Y76R9ATQ)
    Language English
    Publishing date 2006-04-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 1161284-8
    ISSN 1464-3391 ; 0968-0896
    ISSN (online) 1464-3391
    ISSN 0968-0896
    DOI 10.1016/j.bmc.2005.11.040
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: 3-(2-Methoxytetrahydrofuran-2-yl)pyrazoles: a novel class of potent, selective cyclooxygenase-2 (COX-2) inhibitors.

    Ranatunge, Ramani R / Earl, Richard A / Garvey, David S / Janero, David R / Letts, L Gordon / Martino, Allison M / Murty, Madhavi G / Richardson, Stewart K / Schwalb, David J / Young, Delano V / Zemtseva, Irina S

    Bioorganic & medicinal chemistry letters

    2004  Volume 14, Issue 24, Page(s) 6049–6052

    Abstract: A series of 3-(2-methoxytetrahydrofuran-2-yl)pyrazoles (4-10) was synthesized. The compounds were evaluated for their ability to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activity in human whole blood (HWB). The compound, 5-(4- ... ...

    Abstract A series of 3-(2-methoxytetrahydrofuran-2-yl)pyrazoles (4-10) was synthesized. The compounds were evaluated for their ability to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activity in human whole blood (HWB). The compound, 5-(4-methanesulfonylphenyl)-3-(2-methoxytetrahydrofuran-2-yl)-1-p-tolyl-1H-pyrazole 5 showed potent and selective COX-2 inhibition (IC50 for COX-1: >100 microM and COX-2: 1.2 microM).
    MeSH term(s) Cyclooxygenase 1 ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors/chemical synthesis ; Cyclooxygenase Inhibitors/chemistry ; Cyclooxygenase Inhibitors/pharmacology ; Drug Evaluation, Preclinical ; Humans ; Isoenzymes/antagonists & inhibitors ; Membrane Proteins ; Molecular Structure ; Prostaglandin-Endoperoxide Synthases/blood ; Prostaglandin-Endoperoxide Synthases/drug effects ; Pyrazoles/chemical synthesis ; Pyrazoles/chemistry ; Pyrazoles/pharmacology ; Structure-Activity Relationship
    Chemical Substances Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors ; Isoenzymes ; Membrane Proteins ; Pyrazoles ; Cyclooxygenase 1 (EC 1.14.99.1) ; Cyclooxygenase 2 (EC 1.14.99.1) ; PTGS1 protein, human (EC 1.14.99.1) ; PTGS2 protein, human (EC 1.14.99.1) ; Prostaglandin-Endoperoxide Synthases (EC 1.14.99.1)
    Language English
    Publishing date 2004-12-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 1063195-1
    ISSN 1464-3405 ; 0960-894X
    ISSN (online) 1464-3405
    ISSN 0960-894X
    DOI 10.1016/j.bmcl.2004.09.073
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: A comparison of the cyclooxygenase inhibitor-NO donors (CINOD), NMI-1182 and AZD3582, using in vitro biochemical and pharmacological methods.

    Young, Delano V / Cochran, Edward D / Dhawan, Vijay / Earl, Richard A / Ellis, James L / Garvey, David S / Janero, David R / Khanapure, Subhash P / Letts, L Gordon / Melim, Terry L / Murty, Madhavi G / Shumway, Matthew J / Wey, Shiow-Jyi / Zemtseva, Irina S / Selig, William M

    Biochemical pharmacology

    2005  Volume 70, Issue 9, Page(s) 1343–1351

    Abstract: Cyclooxygenase (COX, EC 1.14.99.1) inhibitor-nitric oxide (NO) donor (CINOD) hybrid compounds represent an attractive alternative to NSAID and coxib therapy. This report compares two CINODs, NMI-1182 (naproxen-glyceryl dinitrate) and AZD3582 (naproxen-n- ... ...

    Abstract Cyclooxygenase (COX, EC 1.14.99.1) inhibitor-nitric oxide (NO) donor (CINOD) hybrid compounds represent an attractive alternative to NSAID and coxib therapy. This report compares two CINODs, NMI-1182 (naproxen-glyceryl dinitrate) and AZD3582 (naproxen-n-butyl nitrate), for their ability to inhibit COX-1 and -2, deliver bioavailable nitric oxide, and release naproxen, using in vitro biochemical and pharmacological methods. In human whole blood, both CINODs showed inhibition, comparable to naproxen, of both COX isozymes and slowly released naproxen. Both CINODs donated bioavailable NO, as detected by cGMP induction in the pig kidney transformed cell line, LLC-PK1, but NMI-1182 was more potent by 30-100 times than AZD3582, GTN, GDN, and ISDN and considerably faster in inducing cGMP synthesis than AZD3582. The nitrate groups of GTN, NMI-1182, and AZD3582 appeared to be bioactivated via a common pathway, since each compound desensitized LLC-PK1 cells to subsequent challenge with the other compounds. Similar cGMP induction also occurred in normal, untransformed cells (human renal proximal tubule epithelial cells and hepatocytes from man, rat, and monkey); again, NMI-1182 was superior to AZD3582. NMI-1182 was also the more metabolically labile compound, releasing more absolute nitrate and nitrite (total NO(x)) in human stomach (in which NO is salutary) and liver S9 homogenates. Naproxen was also more rapidly freed from NMI-1182 than AZD3582 in human stomach, although liver S9 hydrolyzed both CINODs with similar rates. These in vitro tests revealed that NMI-1182 may be a better CINOD than AZD3582 because of its superior NO donating and naproxen liberating properties.
    MeSH term(s) Cyclic GMP/biosynthesis ; Cyclooxygenase 1/drug effects ; Cyclooxygenase 2/drug effects ; Cyclooxygenase Inhibitors/pharmacology ; Humans ; Liver/metabolism ; Naphthalenes/pharmacokinetics ; Naphthalenes/pharmacology ; Naproxen/pharmacology ; Nitric Oxide/biosynthesis ; Nitric Oxide Donors/pharmacology
    Chemical Substances Cyclooxygenase Inhibitors ; NMI-1182 ; Naphthalenes ; Nitric Oxide Donors ; naproxen-n-butyl nitrate ; Nitric Oxide (31C4KY9ESH) ; Naproxen (57Y76R9ATQ) ; Cyclooxygenase 1 (EC 1.14.99.1) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Cyclic GMP (H2D2X058MU)
    Language English
    Publishing date 2005-11-01
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 208787-x
    ISSN 1873-2968 ; 0006-2952
    ISSN (online) 1873-2968
    ISSN 0006-2952
    DOI 10.1016/j.bcp.2005.08.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: 3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)(2-pyridyl) phenyl ketone as a potent and orally active cyclooxygenase-2 selective inhibitor: synthesis and biological evaluation.

    Khanapure, Subhash P / Augustyniak, Michael E / Earl, Richard A / Garvey, David S / Letts, L Gordon / Martino, Allison M / Murty, Madhavi G / Schwalb, David J / Shumway, Matthew J / Trocha, Andrzej M / Young, Delano V / Zemtseva, Irina S / Janero, David R

    Journal of medicinal chemistry

    2005  Volume 48, Issue 11, Page(s) 3930–3934

    Abstract: Incorporation of a spacer group between the central scaffold and the aryl ring resulted in a new cyclooxygenase-2 (COX-2) selective inhibitor core structure, 3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)(2-pyridyl) phenyl ketone (20), with COX-2 IC50 = ...

    Abstract Incorporation of a spacer group between the central scaffold and the aryl ring resulted in a new cyclooxygenase-2 (COX-2) selective inhibitor core structure, 3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)(2-pyridyl) phenyl ketone (20), with COX-2 IC50 = 0.25 microM and COX-1 IC50 = 14 microM (human whole blood assay). Compound 20 was orally active in the rat air pouch model of inflammation, inhibiting white blood cell infiltration and COX-2-derived PG production. Our data support the identification of a novel COX-2 selective inhibitor core structure exemplified by 20.
    MeSH term(s) Administration, Oral ; Animals ; Carrageenan ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors/chemical synthesis ; Cyclooxygenase Inhibitors/chemistry ; Cyclooxygenase Inhibitors/pharmacology ; Dinoprostone/antagonists & inhibitors ; Dinoprostone/biosynthesis ; Inflammation/chemically induced ; Inflammation/metabolism ; Male ; Prostaglandin-Endoperoxide Synthases/metabolism ; Pyridines/chemical synthesis ; Pyridines/chemistry ; Pyridines/pharmacology ; Rats ; Rats, Sprague-Dawley ; Sulfones/chemical synthesis ; Sulfones/chemistry ; Sulfones/pharmacology
    Chemical Substances 3-(4-(methylsulfonyl)phenyl)-5-(trifluoromethyl)(2-pyridyl) phenyl ketone ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors ; Pyridines ; Sulfones ; Carrageenan (9000-07-1) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Prostaglandin-Endoperoxide Synthases (EC 1.14.99.1) ; Dinoprostone (K7Q1JQR04M)
    Language English
    Publishing date 2005-06-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/jm0582064
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  6. Article: Structure-based design, synthesis, and biological evaluation of indomethacin derivatives as cyclooxygenase-2 inhibiting nitric oxide donors.

    Wey, Shiow-Jyi / Augustyniak, Michael E / Cochran, Edward D / Ellis, James L / Fang, Xinqin / Garvey, David S / Janero, David R / Letts, L Gordon / Martino, Allison M / Melim, Terry L / Murty, Madhavi G / Richardson, Steward K / Schroeder, Joseph D / Selig, William M / Trocha, A Mark / Wexler, Roseanne S / Young, Delano V / Zemtseva, Irina S / Zifcak, Brian M

    Journal of medicinal chemistry

    2007  Volume 50, Issue 25, Page(s) 6367–6382

    Abstract: Indomethacin, a nonselective cyclooxygenase (COX) inhibitor, was modified in three distinct regions in an attempt both to increase cyclooxygenase-2 (COX-2) selectivity and to enhance drug safety by covalent attachment of an organic nitrate moiety as a ... ...

    Abstract Indomethacin, a nonselective cyclooxygenase (COX) inhibitor, was modified in three distinct regions in an attempt both to increase cyclooxygenase-2 (COX-2) selectivity and to enhance drug safety by covalent attachment of an organic nitrate moiety as a nitric oxide donor. A human whole-blood COX assay shows the modifications on the 3-acetic acid part of the indomethacin yielding an amide-nitrate derivative 32 and a sulfonamide-nitrate derivative 61 conferred COX-2 selectivity. Along with their respective des-nitrate analogs, for example, 31 and 62, the nitrates 32 and 61 were effective antiinflammatory agents in the rat air-pouch model. After oral dosing, though, only 32 increased nitrate and nitrite levels in rat plasma, indicating that its nitrate tether served as a nitric oxide donor in vivo. In a rat gastric injury model, examples 31 and 32 both show a 98% reduction in gastric lesion score compared to that of indomethacin. In addition, the nitrated derivative 32 inducing 85% fewer gastric lesions when coadministered with aspirin as compared to the combination of aspirin and valdecoxib.
    MeSH term(s) Animals ; Aspirin/adverse effects ; Celecoxib ; Cyclooxygenase 2 Inhibitors/adverse effects ; Cyclooxygenase 2 Inhibitors/chemical synthesis ; Cyclooxygenase 2 Inhibitors/pharmacology ; Drug Design ; Drug Synergism ; Female ; Gastric Mucosa/pathology ; Humans ; Hydroxamic Acids/adverse effects ; Hydroxamic Acids/chemical synthesis ; Hydroxamic Acids/pharmacology ; Indomethacin/adverse effects ; Indomethacin/analogs & derivatives ; Indomethacin/chemical synthesis ; Indomethacin/pharmacology ; Male ; Nitric Oxide Donors/adverse effects ; Nitric Oxide Donors/chemical synthesis ; Nitric Oxide Donors/pharmacology ; Pyrazoles/pharmacology ; Rats ; Rats, Sprague-Dawley ; Stomach Ulcer/chemically induced ; Stomach Ulcer/pathology ; Structure-Activity Relationship ; Sulfonamides/pharmacology
    Chemical Substances Cyclooxygenase 2 Inhibitors ; Hydroxamic Acids ; Nitric Oxide Donors ; Pyrazoles ; Sulfonamides ; Celecoxib (JCX84Q7J1L) ; Aspirin (R16CO5Y76E) ; Indomethacin (XXE1CET956)
    Language English
    Publishing date 2007-12-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/jm0611861
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  7. Article: NMI-1182, a gastro-protective cyclo-oxygenase-inhibiting nitric oxide donor.

    Ellis, James L / Augustyniak, Michael E / Cochran, Edward D / Earl, Richard A / Garvey, David S / Gordon, Laura J / Janero, David R / Khanapure, Subhash P / Letts, L Gordon / Melim, Terry L / Murty, Madhavi G / Schwalb, David J / Shumway, Matthew J / Selig, William M / Trocha, A Mark / Young, Delano V / Zemtseva, Irina S

    Inflammopharmacology

    2005  Volume 12, Issue 5-6, Page(s) 521–534

    Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammation and to provide pain relief but suffer from a major liability concerning their propensity to cause gastric damage. As nitric oxide (NO) is known to be gastro-protective ... ...

    Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammation and to provide pain relief but suffer from a major liability concerning their propensity to cause gastric damage. As nitric oxide (NO) is known to be gastro-protective we have synthesized a NO-donating prodrug of naproxen named NMI-1182. We evaluated two cyclo-oxygenase (COX)-inhibiting nitric oxide donors (CINODs), NMI-1182 and AZD3582, for their ability to be gastro-protective compared to naproxen and for their anti-inflammatory activity. NMI-1182 and AZD3582 were found to produce similar inhibition of COX activity to that produced by naproxen. Both NMI-1182 and AZD3582 produced significantly less gastric lesions after oral administration than naproxen. All three compounds effectively inhibited paw swelling in the rat carrageenan paw edema model. In the carrageenan air pouch model all three compounds significantly reduced PGE2 levels in the pouch exudate but only NMI-1182 and naproxen inhibited leukocyte influx. These data demonstrate that NMI-1182 has comparable anti-inflammatory activity to naproxen but with a much reduced likelihood to cause gastric damage.
    MeSH term(s) Animals ; Anti-Inflammatory Agents/blood ; Anti-Inflammatory Agents/chemistry ; Anti-Inflammatory Agents/pharmacology ; Aorta, Abdominal/drug effects ; Aorta, Abdominal/physiology ; Carrageenan ; Cyclooxygenase 1/blood ; Cyclooxygenase 2/blood ; Cyclooxygenase Inhibitors/blood ; Cyclooxygenase Inhibitors/chemistry ; Cyclooxygenase Inhibitors/pharmacology ; Dinoprostone/antagonists & inhibitors ; Dinoprostone/metabolism ; Dose-Response Relationship, Drug ; Edema/chemically induced ; Edema/prevention & control ; Gastric Mucosa/drug effects ; Gastric Mucosa/metabolism ; Gastric Mucosa/pathology ; Humans ; In Vitro Techniques ; Inflammation/chemically induced ; Inflammation/prevention & control ; Male ; Molecular Structure ; Naphthalenes/blood ; Naphthalenes/chemistry ; Naphthalenes/pharmacology ; Naproxen/blood ; Naproxen/chemistry ; Naproxen/pharmacology ; Neutrophil Infiltration/drug effects ; Nitric Oxide Donors/blood ; Nitric Oxide Donors/chemistry ; Nitric Oxide Donors/pharmacology ; Protective Agents/chemistry ; Protective Agents/pharmacology ; Rats ; Rats, Sprague-Dawley ; Vasodilation/drug effects
    Chemical Substances Anti-Inflammatory Agents ; Cyclooxygenase Inhibitors ; NMI-1182 ; Naphthalenes ; Nitric Oxide Donors ; Protective Agents ; des-NO-NMI-1182 ; naproxen-n-butyl nitrate ; Naproxen (57Y76R9ATQ) ; Carrageenan (9000-07-1) ; Cyclooxygenase 1 (EC 1.14.99.1) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Dinoprostone (K7Q1JQR04M)
    Language English
    Publishing date 2005
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1080058-x
    ISSN 1568-5608 ; 0925-4692
    ISSN (online) 1568-5608
    ISSN 0925-4692
    DOI 10.1163/156856005774382661
    Database MEDical Literature Analysis and Retrieval System OnLINE

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