Skip to main content

The discovery, development and novel actions of nimesulide

  • Chapter

Conclusions

Nimesulide has a variety of potentially novel, non-pain, effects some of which may be related to its known pharmacological actions relating to its anti-inflammatory effects. The effects of the drug on intracellular signalling pathways that regulate cell growth and other cellular controls may represent some unique sites of action of the drug.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Otterness IG (1995) The discovery of drugs to treat arthritis: A historical view. In: VJ Merluzzi, J Adams (eds): The search for anti-inflammatory Drugs. Birkhäuser, Boston, 1–26

    Google Scholar 

  2. Rainsford KD (2004) History and development of the salicylates. In: K D Rainsford (ed): Aspirin and related drugs. Taylor and Francis, London, 1–23

    Google Scholar 

  3. McTavish JR (2004) The industrial history of analgesics: the evolution of analgesics and antipyretics. In: K D Rainsford (ed): Aspirin and related drugs. Taylor and Francis, London, 25–43

    Google Scholar 

  4. Prescott LF (2001) Paracetamol (Acetaminophen). A Critical Bibliographic Review. Taylor and Francis, London

    Google Scholar 

  5. Rainsford KD (1999) History and development of ibuprofen. In: KD Rainsford (ed): Ibuprofen. A critical bibliographic review. Taylor and Francis, London, 1–24

    Google Scholar 

  6. Vane JR (1971) Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature 231: 232–235

    CAS  Google Scholar 

  7. Müller W, Harwerth H-G, Fehr K (eds) (1971) Rheumatoid Arthritis. Pathogenic Mechanisms and Consequences in Therapeutics. Academic Press, London & New York

    Google Scholar 

  8. Smith MJH, Smith PK (eds) (1966) The salicylates. A critical bibliographic review. Wiley Interscience, New York, London & Sydney

    Google Scholar 

  9. Whitehouse MW (1968). The molecular pharmacology of anti-inflammatory drugs: some possible mechanisms of action at the biochemical level. Biochem Pharmacol Suppl: 293–307

    Google Scholar 

  10. Giroud JP, Willoughby DA, Velo, GP (eds) (1975) Future trends in inflammation II. Bikhä user Verlag, Basel & Stuttgart

    Google Scholar 

  11. Weissman G (1992) Inflammation. Historical perspective. In: Gallin J, Goldstein IM, Snyderman R (eds): Inflammation: Basic principles and clinical correlates. 2 nd Edition. Ravel Press, New York, 5–9

    Google Scholar 

  12. Moore, GGI (1974) Sulfonamides with anti-inflammatory activity. In: Scherrer, RA, Whitehouse MW (eds): Antiinflammatory agents. Chemistry and pharmacology, Volume 1. Academic Press, New York, San Francisco & London, 160–177

    Google Scholar 

  13. Rainsford KD (2004) Occurrence, properties and synthetic developments of the salicylates. In: Rainsford KD (ed): Aspirin and related drugs. Taylor and Francis, London, 45–96

    Google Scholar 

  14. Moore GGI, Harrington JK (1974) Substituted 3-phenoxy alkane sulphonanilides. US Patent No. 3,840,597, October 8, 1974

    Google Scholar 

  15. Vigdahl RL, Tukey RH (1977) Mechanism of action of novel anti-inflammatory drugs diflumidone and R-805. Biochem Pharmacol 26: 307–311

    Article  PubMed  CAS  Google Scholar 

  16. Swingle KF, Hamilton RR, Harrington JK, Kvam DC (1971) 3-Benzoyldifluoromethanesulfonanilide, sodium salt (diflumidone sodium, MBR 416408): a new anti-inflammatory agent. Arch Int Pharmacodyn Ther 189: 129–144

    PubMed  CAS  Google Scholar 

  17. Swingle KF, Moore GGI, Grant TJ (1976) 4-Nitro-2-phenoxymethanesulfonanilide (R-805): a chemically novel anti-inflammatory agent. Arch Int Pharmacodyn Ther 221: 132–139

    PubMed  CAS  Google Scholar 

  18. Rufer C, Schillinger E, Böttcher I, Repenthin W, Herrmann CH (1982) Non-steroidal anti-inflammatories-XII. Mode of action of anti-inflammatory methane sulfonanilides. Biochem Pharmacol 31: 3591–3596

    Article  PubMed  CAS  Google Scholar 

  19. Kuehl FA, Humes JL, Egan RW, Ham EA, Beveridge GC, van Arman CG (1977). Role of prostaglandin endoperoxide PGG2 in inflammatory processes. Nature 265: 170–173

    Article  PubMed  CAS  Google Scholar 

  20. Riker Lab Inc (1975). p-Nitration of alkane sulfonanilides, by careful treatment with nitration agent in at least equimolar amt. WPI Acc No. 1975-01873W/197501

    Google Scholar 

  21. Cignarella G, Vianello P, Berti F, Rossoni G (1996) Synthesis and pharmacological evaluation of derivatives structurally related to nimesulide. Eur J Med Chem 31: 359–364

    Article  CAS  Google Scholar 

  22. Kensai Y, Saito M, Masami G, (with Taisho Pharmaceutical Co Ltd) (1997) Japanese PCT Application No. WO 9746520

    Google Scholar 

  23. Yoshinari Y, Yutaka O, Kazuto S, Hideji S, Katsuo H (1998) Preparation of sulfonanilide derivatives as anti-inflammatory agents. Japanese Kokai Tokkyo Koho-Japanese Patent JP 02022260

    Google Scholar 

  24. Fernandes AC daS, Borges JER, Pereira MFBM da S, Romao CJC, Correia LMB, Correia PB (1999) Method for the preparation of aryl ethers using silver salt as catalyst under ultrasound irradiation. Portugese Patent Application No. PT 1999-102315

    Google Scholar 

  25. Bangyin C, Hanping Z, Lihong Z, Xinfen Z, Zhenguo Z, Shugang G, Hong L (2000) Synthesis and structural identification of nonsteroidal anti-inflammatory drug nimesulide. Tongji Yike Daxue Xuebao [Acta Univ Med Tongji] 29: 67–68

    Google Scholar 

  26. Attal V, Belsare DP (2003) Synthesis and anti-inflammatory activity of arylsulfonanilides structurally related to nimesulide. Ind J Pharmaceut Sci 65: 135–138

    CAS  Google Scholar 

  27. Singla AK, Chawla M, Singh A (2000) Review. Nimesulide: some pharmaceutical and pharmacological aspects — An update. J Pharm Pharmacol 52: 467–486

    Article  PubMed  CAS  Google Scholar 

  28. British Pharmacopoeia, Vol II (2004). Nimesulide. The Stationery Office, London, 1378–1379

    Google Scholar 

  29. Fallavena PRB, Schapovral EES (1997) pKa determination of nimesulide in methanolwater mixtures by potentiometric titration. Int J Pharm 158: 109–112

    Article  CAS  Google Scholar 

  30. Singh S, Sharda N, Mahajan L (1999) Spectrophotometric determination of pKa of nimesulide. Int J Pharm 176: 261–264

    Article  CAS  Google Scholar 

  31. Piel G, Pirotte I, Delneuville I, Neven P, Llabres G, Delarge J, Delattre L (1997) Study of the influence of both cyclodextrins and L-lysine on the aqueous solubility of nimesulide: isolation and characterization of nimesulide-L-lysine-cyclodextrin complexes. J Pharm Sci 86: 475–480

    Article  PubMed  CAS  Google Scholar 

  32. Seedher N, Bhatia S (2003) Solubility enhancement of Cox-2 inhibitors using various solvent systems. AAPS PharmSciTech 4: 1–9

    Article  Google Scholar 

  33. Dupont L, Pirotte B, Masereel B, Delarge J, Geczy J (1995) Nimesulide. Acta Cryst C51: 507–509

    CAS  Google Scholar 

  34. Iley J, Lopes F, Moreira R (2001) Kinetics and mechanism of hydrolysis of N-amidomethylsulfonamides. J Chem Soc, Perkin Trans 2: 749–753

    Google Scholar 

  35. Chang SF, Miller AM, Ober RE (1977) Determination of an anti-inflammatory methanesulfonanilide in plasma by high-speed liquid chromatography. J Pharm Sci 66: 1700–1703

    PubMed  CAS  Google Scholar 

  36. Carini M, Aldini G, Stefani R, Marinello C, Facino RM (1998) Mass-spectrometric characterization and HPLC determination of the main urinary metabolites of nimesulide in man. J Pharm Biomed Anal 18: 201–211

    Article  PubMed  CAS  Google Scholar 

  37. Barrientos-Astigarraga RE, Vannuchi YB, Sucupira M, Moreno RA, Muscara MN, De Nucci G (2001). Quantification of nimesulide in human plasma by high-performance liquid chromatography/tandem mass spectrometry. Application to bioequivalence studies. J Mass Spectrom 36: 1281–1286

    Article  PubMed  CAS  Google Scholar 

  38. Macpherson D, Best SA, Gedik L, Hewson AT, Rainsford KD, Parisi S (2004) The biotransformation and pharmacokinetics in humans of nimesulide. Submitted

    Google Scholar 

  39. Alvarez-Lueje A, Vásquez-Vergara P. Núñez-Vergara LJ, Squella JA (1998) HPLC determination of nimesulide in tablets by electrochemical detection. Anal Lett 31: 1173–1184

    CAS  Google Scholar 

  40. Lakshmi CSR, Reddy MN, Naidu PY (1998) Fluorimetric determination of nimesulide with N-(1-naphthyl) ethylene. Indian Drugs 35: 519–520

    CAS  Google Scholar 

  41. Altinöz S, Dursun ÖÖ (2000) Determination of nimesulide in pharmaceutical dosage forms by second order derivative UV spectrometry. J Pharm Biomed Anal 22: 175–182

    PubMed  Google Scholar 

  42. Chandran S, Saggar S, Priya KP, Saha RN (2000) New ultraviolet spectrophotometric method for the estimation of nimesulide. Drug Dev Ind Pharm 26: 229–234

    Article  PubMed  CAS  Google Scholar 

  43. Patravale VB, D’souza S, Narkar Y (2001) HPTLC determination of nimesulide from pharmaceutical dosage forms. J Pharm Biomed Anal 25: 685–688

    Article  PubMed  CAS  Google Scholar 

  44. Macnaughton SJ, Kikic I, Foster NR, Alessi P, Cortesi A, Colombo I (1996) Solubility of anti-inflammatory drugs in supercritical carbon dioxide. J Chem Eng Data 41: 1083–1086

    Article  CAS  Google Scholar 

  45. Catarino RI, Conceicao AC, Garcia MB, Goncalves ML, Lima JL, dos Santos MM (2003) Flow amperometric determination of pharmaceuticals with on-line electrode surface renewal. J Pharm Biomed Anal 33: 571–580

    Article  PubMed  CAS  Google Scholar 

  46. Maffei Facino R, Carini M, Aldini G, Saibene L, Morelli R (1995) Differential inhibition of superoxide, hydroxyl and peroxyl radicals by nimesulide and its main metabolite 4-hydroxynimesulide. Arzneim-Forsch 45(II): 10–17

    Google Scholar 

  47. Facino RM, Carini M, Aldini G (1993) Antioxidant activity of nimesulide and its main metabolites. Drugs 46(Suppl 1): 15–21

    PubMed  Google Scholar 

  48. Maffei Facino R, Carini M, Aldini G, Saibene L, Macciocchi A (1993) Antioxidant profile of nimesulide, indomethacin and diclofenac in phosphatidylcholine liposomes (PCL) as membrane model. Int J Tissue React 15: 225–234

    CAS  Google Scholar 

  49. Karunakar N, Prabhakar MC, Krishnar DR (2003) Determination of the antioxidant activity of some drugs using high-pressure liquid chromatography. Arzneim-Forsch 53: 254–259

    CAS  Google Scholar 

  50. Mouithys-Mickalad AM, Zheng SX, Deby-Dupont GP, Deby CM, Lamy MM, Reginster JY, Henrotin YE (2000) In vitro study of the antioxidant properties of non-steroidal anti-inflammatory drugs by chemiluminescence and electron spin resonance (ESR). Free Radic Res 33: 607–621

    PubMed  CAS  Google Scholar 

  51. Kovarikova P, Mokry M, Klimes J (2003) Photochemical stability of nimesulide. J Pharm Biomed Anal 26: 827–832

    Google Scholar 

  52. Rainsford KD (1992) Mechanisms of rash formation and related skin conditions induced by non-steroidal anti-inflammatory drugs. In: Rainsford KD, Velo GP (eds): Side-effects of Anti-inflammatory Drugs 3. Kluwer Academic Publishers, Lancaster, 287–301

    Google Scholar 

  53. Moore DE (2002) Drug-induced cutaneous photosensitivity: incidence, mechanism, prevention and management. Drug Saf 25: 345–372

    PubMed  CAS  Google Scholar 

  54. Squella JA, Gonzalez P, Bollo S, Nunez-Vergara LJ (1999) Electrochemical generation and interaction study of the nitro radical anion from nimesulide. Pharm Res 16: 161–164

    Article  PubMed  CAS  Google Scholar 

  55. Van Antwerpen P, Dubois J, Gelbeke M, Neve J (2004) The reactions of oxicam and sulfonanilide non steroidal anti-inflammatory drugs with hypochlorous acid: determination of the rate constants with an assay based on the competition with para-aminobenzoic acid chlorination and identification of some oxidation products. Free Radic Res 38: 251–258

    PubMed  Google Scholar 

  56. Florence AT, Jani PU (1994) Novel oral drug formulations. Their potential in modulating adverse effects. Drug Saf 10: 233–266

    PubMed  CAS  Google Scholar 

  57. Redenti E, Szente L, Szejtli J (2001) Cyclodextrin complexes of salts of acidic drugs. Thermodynamic properties, structural features, and pharmaceutical applications. J Pharm Sci 90: 979–986

    Article  PubMed  CAS  Google Scholar 

  58. Bonardelli P, Oliani C, Monici Preti PA, Pellicano P, Quattrocchi G (1990) Efficacy and gastrointestinal tolerability of beta-cyclodextrin-piroxicam and tenoxicam in the treatment of chronic osteoarthritis. Clin Ther 12: 547–555

    PubMed  CAS  Google Scholar 

  59. Santucci L, Fiorucci S, Chiucchi S, Sicilia A, Bufalino L, Morelli A (1992) Placebo-controlled comparison of piroxicam-beta-cyclodextrin, piroxicam, and indomethacin on gastric potential difference and mucosal injury in humans. Dig Dis Sci 37: 1825–1832

    Article  PubMed  CAS  Google Scholar 

  60. Wang D, Miller R, Zheng J, Hu C (2000) Comparative population pharmacokinetic pharmacodynamic analysis for piroxicam-beta-cyclodextrin and piroxicam. J Clin Pharmacol 40: 1257–1266

    PubMed  CAS  Google Scholar 

  61. Pijak MR, Turcani P, Turcaniova Z, Buran I, Gogolak I, Mihal A, Gazdik F (2002) Efficacy and tolerability of piroxicam-beta-cyclodextrin in the outpatient management of chronic back pain. Bratisl Lek Listy 103: 467–472

    PubMed  CAS  Google Scholar 

  62. Mester U, Lohmann C, Pleyer U, Steinkamp G, Volcker E, Kruger H, Raj PS (2002) A comparison of two different formulations of diclofenac sodium 0.1% in the treatment of inflammation following cataract-intraocular lens surgery. Drugs RD 3: 143–151

    Article  CAS  Google Scholar 

  63. Scolari G, Lazzarin F, Fornaseri C, Carbone V, Rengo S, Amato M, Cicciu D, Braione D, Argentino S, Morgantini A et al (1999) A comparison of nimesulide beta cyclodextrin and nimesulide in postoperative dental pain. Int J Clin Pract 53: 345–348

    PubMed  CAS  Google Scholar 

  64. Raja M, Sivaseelam A, Subbiah R, Yuvaraj NR, Chandran K, Annamalai K (2001) Evaluation of efficacy and safety of nimesulide with betacyclodextrin vs nimesulide tablets in osteoarthritis. J Indian Med Assoc 99: 451–452

    PubMed  CAS  Google Scholar 

  65. Fioravanti A, Storri L, Di Martino S, Bisogno S, Oldani V, Scotti A, Marcolongo R (2002) A randomized, double-blind, multicentre trial of nimesulide-beta-cyclodextrin versus naproxen in patients with osteoarthritis. Clin Ther 24: 504–519

    Article  PubMed  CAS  Google Scholar 

  66. Dasgupta KS, Deshpande AS, Vedi JN, Patel S (2002) Evaluation of efficacy of nizer versus nimesulide tablets in otitis media. J Indian Med Assoc 100: 619

    PubMed  CAS  Google Scholar 

  67. Dubini E, Vidi A, Bietti G, Maffione G (1991) Inclusion compounds of nimesulide with cyclodextrins. Boehringer Ingelheim Italia (IT). Patent No. WO 9117774

    Google Scholar 

  68. Sicart Girona I (1991) Inclusion complexes with cyclodextrins. Leetrim Ltd., German Offen., German Patent, DE 1991-4116659

    Google Scholar 

  69. Geczy J (1998) Nimesulide salt cyclodextrin inclusion complexes. Europharmaceutical S.A., Cyclolab Cyclodextrin Research. US Patent No. US 5744165

    Google Scholar 

  70. Vavia PR, Adhage NA (1999) Inclusion complexation of nimesulide with beta-cyclodextrins. Drug Dev Ind Pharm 25: 543–545

    Article  PubMed  CAS  Google Scholar 

  71. Adhage NA, Vavia PR (2000) b-Cyclodextrin inclusion complexation by milling. Pharm Pharmacol Commun 6: 13–17

    CAS  Google Scholar 

  72. Chowdary KP, Nalluri BN (2000) Nimesulide and beta-cyclodextrin inclusion complexes: physicochemical characterization and dissolution rate complexes. Drug Dev Ind Pharm 26: 1217–1220

    PubMed  CAS  Google Scholar 

  73. Nalluri BN, Chowdary KP, Murthy KV, Hayman AR, Becket G (2003) Physicochemical characterization and dissolution properties of nimesulide-cyclodextrin binary systems. AAPS PharmSciTech 4: E2

    Article  PubMed  Google Scholar 

  74. Margarotto L, Berini S, Cosentino C, Torri G (2000–2001) Characterization of nimesulide/beta-cyclodextrin composite obtained by solid state activation. Metastable Mech Alloyed Nanocryst Materials 360-3: 643–648

    Google Scholar 

  75. Miro A, Quaglia F, Calignano A, Barbato F, Cappello B, La Rotonda MI (2000) Physicochemical and pharmacological properties of nimesulide/beta-cyclodextrin formulations. STP Pharma Sci 10: 157–164

    CAS  Google Scholar 

  76. Ravelet C, Geze A, Villet A, Grosset C, Ravel A, Wouessidjewe D, Peyrin E (2002) Chromatographic determination of the association constants between nimesulide and native and modified beta-cyclodextrins. J Pharm Biomed Anal 29: 425–430

    Article  PubMed  CAS  Google Scholar 

  77. Braga SS, Ribeiro-Claro P, Pillinger M, Goncalves IS, Pereira F, Fernades AC, Correia PB, Teixeira-Dias JJ (2003) Encapsulation of sodium nimesulide and precursors in betacyclodextrin. Org Biomol Chem 1: 873–878

    Article  PubMed  CAS  Google Scholar 

  78. Jain R, Singh A (1997) Pharmaceutical injectable analgesic composition containing nimesulide. Panacea Biotec Ltd, India. US Patent No. US 5,688,829. European Patent No.EP 0812591(1997). Australia Patent No. AU 69,320 (1998). Canadian Patent No.

    Google Scholar 

  79. Geczy J, Neven P, Piel G, Pirotte B, Delneuville I (1998) Water-soluble nimesulide salt and its preparation, aqueous dilution containing it, nimesulide-based combinations and their uses. US Patent No. US 5756546

    Google Scholar 

  80. De Tommaso V (1999) A water soluble nimesulide adduct also for injectable use. Micio Pharma Chemica Aktienge. Patent No. WO 9941233

    Google Scholar 

  81. Singh A, Jain R (1999) Water-miscible nonsteroidal antiinflammatory injections. Panacea Biotech Ltd, India. Patent No. JP 11228448

    Google Scholar 

  82. Grassi M, Coceani N, Mararotto L (2002) Modelling partitioning of sparingly soluble drugs in a two-phase system. Int J Pharm 239: 157–169

    Article  PubMed  CAS  Google Scholar 

  83. Ferreira H, Lucio M, de Catro B, Gameiro P, Lima JL, Reis S (2003) Partition and location of nimesulide in EPC liposomes: a spectrophotometric and fluorescence study. Anal Bioanal Chem 377: 293–298

    PubMed  CAS  Google Scholar 

  84. Jain R, Singh A (2001) Effervescent compositions comprising nimesulide. Panacea Biotec Ltd, India. Patent No. WO0122917

    Google Scholar 

  85. Giorgetti PLM (2001) Pharmaceutical preparation containing nimesulide for oral administration. Errekappa Euroterapici SPA. Patent No. US 6194462

    Google Scholar 

  86. Monti T, Mossi W (1999) Nimesulide micronized salts. Helsinn Healthcare SA. Patent No. EP O937709

    Google Scholar 

  87. Skinhoj A, Bertelsen P (1998) Modified-release multiple-units compositions of nonsteroid anti-inflammatory drugs. Nycomed Danmark A/S, Denmark. WO 9912524

    Google Scholar 

  88. Jain R, Singh A (2001) Controlled release compositions comprising nimesulide. Panacea Biotec Ltd, India. Patent No. WO 0122791

    Google Scholar 

  89. Uhrich K, Macedo B (2001) Therapeutic compositions containing anti-inflammatory agents and biodegradable polyanhydrides. Rutgers, The State University of New Jersey. Patent No. WO 2001041753

    Google Scholar 

  90. Lai C-S, Wang T (2002) Modified forms of pharmacologically active agents for use as nonsteroidal anti-inflammatory drugs (NSAIDs). Medinox Inc, USA. Patent No. WO 2002000167

    Google Scholar 

  91. Martino AC, Noack RM, Pierman SA (2004) Coated pharmaceutical tablets with speckled appearance. Pharmacia Corporation, USA. Patent No. WO 2003066030

    Google Scholar 

  92. Garg S, Verma RK, Kaul CL (2003) Pharmaceutical composition for extended/sustained release of therapeutically active ingredient. Council of Scientific and Industrial Research, India. Patent No. WO 2003063825

    Google Scholar 

  93. Tandon P, Mishra B (2004) Development of multiple w/o/w emulsions showing prolonged antiinflammatory activity of nimesulide. Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi, 221005, India

    Google Scholar 

  94. Biyani MK, Jathar SR, Acharya MM (2001) A controlled release anti-inflammatory nimesulide formulation. Ajanta Pharma Limited, India. Patent No. WO 2001097775

    Google Scholar 

  95. Vandelli MA, Ruozi B, Forni F (1999) PLA microparticles for the prologed release of nimesulide: effect of preparative variables. STP Pharma Sci 9: 567–572

    CAS  Google Scholar 

  96. De Angelis P, Olivieri A (2002) Method of increasing the bioavailability of nimesulide. Bioprogress Spa, Italy. Patent No. EP 1258241

    Google Scholar 

  97. Ishii K, Yamada R, Ito J, Nemoto M (2004) Solid oral preparations containing sulfonamide-based anti-inflammatory agents with improved absorbability. Taisho Pharma Co Ltd, Japan. Patent No. JP 08127533

    Google Scholar 

  98. Borsa M (1997) Oral pharmaceutical composition having antipyretic, analgesic and anti-inflammatory activity. Leetrim Ltd, UK. Patent No. EP 843998

    Google Scholar 

  99. Sato M, Hizaki M, Tada Y, Yamada M (2004) Solid preparations of anti-inflammatory nimesulide or its analogs with improved absorption in digestive tract. Hisamitsu Pharmaceutical Co., Japan. Patent No. JP 09202728

    Google Scholar 

  100. Moroni E (1997) Non-stomach-harming and/or controlled release pharmaceutical composition based on nimesulide which can be administered orally. Aesculapius Farma SRL. Patent No. IT 1270958

    Google Scholar 

  101. Mutalik S, Venkates, Udupa N (2004) Fast analgesic activity from recrystallized nimesulide and its solid dispersion. Ind J Physiol Pharmacol 46: 115–118

    Google Scholar 

  102. Jain R, Singh A (1999) Pharmaceutical compositions containing NSAIDs and piperine. Panacea Biotec Ltd, India. Patent No. EP 0935964

    Google Scholar 

  103. Agrawal S, Pancholi SS, Jain NK, Agrawal GP (2004) Hydrotropic solubilization of nimesulide for parenteral administration. Int J Pharm 274: 149–155

    Article  PubMed  CAS  Google Scholar 

  104. Garces Garces J, Bonilla Munoz A, Parente Duena A (1998) Pharmaceutical preparation comprising coated capsules or tablets containing a liposome powder encapsulating a drug. European Patent No EP 855179

    Google Scholar 

  105. Miyata S, Taniguchi Y, Masuda K, Kawamura Y (1995) Antiinflammatory agent for external use. Hisamitsu Pharmaceutical Co Inc, Japan. Patent No. WO 9611002

    Google Scholar 

  106. Jain R, Singh A (1996) Therapeutic anti-inflammatory and analgesic composition containing nimesulide for transdermal use. Panacea Biotec Ltd, India. Patent No. US 5716609

    Google Scholar 

  107. Jain R, Singh A (1997) Transdermal compositions containing nimesulide. Panacea Biotec Ltd, India. Patent No. EP 0812587

    Google Scholar 

  108. Taniguchi Y, Miyata S, Kawamura Y, Mauda K (1997) Antiinflammatory agent for external use. Helsinn Healthcare SA, Switzerland. Patent No. EP 0782855

    Google Scholar 

  109. Jain R, Singh A (1997) Transdermal compositions containing nimesulide. Panacea Biotec Ltd, India. Patent No. EP 0812587

    Google Scholar 

  110. Valenti M, Fabiani F, Frimonti EA (2000) Topical compositions containing a non-steroidal antiinflammatory drug. Farmaceutici Formenti SpA, Italy. Patent No. WO 2000048588

    Google Scholar 

  111. Di Schiena MG (1998) Topical pharmaceutical formulations containing nimesulide. Dompe Int Sam (MC). Patent No. EP 0880965

    Google Scholar 

  112. Giorgetti PLM (1999) Pharmaceutical preparation containing nimesulide for topical use. Errekappa Eurotherapici SPA (IT). Patent No. US 5998480

    Google Scholar 

  113. Embil K, Figueroa R (2000) Nimesulide containing topical pharmaceutical compositions. Edko Trading Representation. Patent No. WO 0009117

    Google Scholar 

  114. Pedrani M, Ajani M, Villa R (2000) Pharmaceutical compositions for the topical administration in the oral cavity of on-steroid anti-inflammatory drugs useful for the stomatologic, mouth and oral cavity anti-inflammatory and analgesic therapies. Farmatron Limited, UK. Patent No. WO 2001049276

    Google Scholar 

  115. Giannaccini B, Saettone MF, Monti D, Boldrini E, Farmigea S, Bianchini P (2000) Use of niaouli essential oil as transdermal permeation enhancer. Patent No. WO 0053228

    Google Scholar 

  116. Sengupta S, Velpandian T, Sapra P, Mathur P, Gupta S (1998) Comparative analgesic efficacy of nimesulide and diclofenac gels after topical application on the skin. Skin Pharmacol Appl Skin Physiol 11: 273–278

    Article  PubMed  CAS  Google Scholar 

  117. Jain NK, Kulkarni SK (2001) Pharmacological and pharmacokinetic studies on marketed gel formulations of nimesulide. Indian Drugs 38: 63–66

    Google Scholar 

  118. Anonymous (2000) Nimesulide Gel. Adis International Ltd, Milano

    Google Scholar 

  119. Jain R, Singh A (1998) Novel therapeutic anti-inflammatory and analgesic composition containing nimesulide for use transdermally and process for manufacture thereof. Panancea Biotec Ltd, India. Canadian Patent No. CN 1189337

    Google Scholar 

  120. Giorgetti PLM (1999) Pharmaceutical preparation containing nimesulide for topical use. Errekappa Eurotherapici SPA, Italy. US Patent No. US 5998480

    Google Scholar 

  121. Bader S, Monti T, Hausermann E (2001) Nimesulide topical formulations in the form of liquid crystals. Helsinn Healthcare SA, Switzerland. US Patent No. US 6288121

    Google Scholar 

  122. Bader S, Monti T, Hausermann E (2003) Nimesulide gel systems for topical use. Helsinn Healthcare SA, Switzerland. US Patent No. US 2003036563

    Google Scholar 

  123. Monti T, Bader S, Hausermann E (2002) Nimesulide gel systems for topical use. US Patent No. US 2002119997

    Google Scholar 

  124. Shahiwala A, Misra A (2002) Studies in topical application of niosomally entrapped nimesulide. J Pharm Pharmaceut Sci 5: 220–225

    CAS  Google Scholar 

  125. Khandare JN, Hemant JB, Ramesh UR (2004) Preparation and evaluation of nimesulide niosomes for topical application. Indian Drugs 38: 197–202

    Google Scholar 

  126. Bennett A, Charlier EM, McDonald AM, Simpson JS, Stamford IF, Zebro T (1977) Prostaglandins and breast cancer. Lancet 2: 624–626

    PubMed  CAS  Google Scholar 

  127. Bennett A, Tacca MD, Stamford IF, Zebro T (1977) Prostaglandins from tumours of human large bowel. Br J Cancer 35: 881–884

    PubMed  CAS  Google Scholar 

  128. Bennett A (1976) Prostaglandins as factors in diseases of the alimentary tract. Adv Prostagl Thromb Res 2: 547–555

    CAS  Google Scholar 

  129. Thun MJ, Henley SJ (2003) Epidemiology of nonsteroidal anti-inflammatory drugs and colorectal cancer. In: Harris RE (ed): COX-2 Blockade in Cancer Prevention and Therapy. Human Press, Totawa, New Jersey, 35–55

    Google Scholar 

  130. Rüegg C, Zaric J, Stupp R (2003) Non steroidal anti-inflammatory drugs and COX-2 inhibitors as anti-cancer therapeutics: hypes, hopes and reality. Ann Med 35: 476–487

    PubMed  Google Scholar 

  131. Harris RE (Ed) (2003) COX-2 Blockade in Cancer Prevention and Therapy. Humana Press, Totowa, New Jersey

    Google Scholar 

  132. Rainsford KD (2004) Aspirin and NSAIDs in the prevention of cancer, Alzheimer’s disease and other novel therapeutic actions. In: Rainsford KD (ed): Aspirin and Related Drugs. CRC Press, Boca Raton (Florida), 707–755

    Google Scholar 

  133. Roche-Nagle G, Connolly EM, Eng M, Bouchier-Hayes DJ, Harmey JH (2004) Antimetastatic activity of a cyclooxygenase-2 inhibitor. Br J Cancer 91: 359–365

    PubMed  CAS  Google Scholar 

  134. Koehne CH, Dubois RN (2004) COX-2 inhibition and colorectal cancer. Semin Oncol 31(Suppl 7): 12–21

    PubMed  CAS  Google Scholar 

  135. Altorki NK, Subaramaiah K, Dannenberg AJ (2004) COX-2 inhibition in upper aerodigestive tract tumours. Semin Oncol 31(Suppl 7): 30–36

    PubMed  CAS  Google Scholar 

  136. Liao Z, Milas L (2004) COX-2 and its inhibition as a molecular target in the prevention and treatment of lung cancer. Expert Rev Anticancer Ther 4: 543–560

    Article  PubMed  CAS  Google Scholar 

  137. Mann JR, DuBois RN (2004) Cyclooxygenase-2 and gastrointestinal cancer. Cancer J 10: 145–152

    Article  PubMed  CAS  Google Scholar 

  138. Peek RM Jr (2004) Prevention of colorectal cancer through the use of COX-2 selective inhibitors. Cancer Chemother Pharmacol 54(Suppl 1): S50–S56

    PubMed  CAS  Google Scholar 

  139. Charalambous D, O’Brien PE (1996) Inhibition of colon cancer precursors in the rat by sulindac sulphone is not dependent on inhibition of prostaglandin synthesis. J Gastroenterol Hepatol 11: 307–310

    PubMed  CAS  Google Scholar 

  140. Schnitzler M, Dwight T, Robinson BG (1996) Sulindac increases the expression of APC mRNA is malignant colonic epithelial cells: an in vitro study. Gut 38: 707–713

    PubMed  CAS  Google Scholar 

  141. Duffy CP, Elliott CJ, O’Connor RA, Heenan MM, Coyle S, Cleary IM, Kavanagh K, Verhaegen S, O’ Loughlin CM, NicAmlaoibh R, Clynes M (1998) Enhancement of chemotherapeutic drug toxicity to human tumour cells in vitro by a subset of nonsteroidal anti-inflammatory drugs (NSAIDs). Eur J Cancer 34: 1250–1259

    Article  PubMed  CAS  Google Scholar 

  142. Zhang Z, DuBois RN (2000) Par-4, a proapoptotic gene, is regulated by NSAIDs in human colon carcinoma cells. Gastroenterology 118: 1012–1017

    Article  PubMed  CAS  Google Scholar 

  143. Karacay B, Sanlioglu S, Griffith TS, Sandler A, Bonthius DJ (2004) Inhibition of the NF-κB pathway enhances TRAIL-mediated apoptosis in neuroblastoma cells. Cancer Gene Therapy 11: 681–690

    Article  PubMed  CAS  Google Scholar 

  144. Kazhdan I, Marciniak RA (2004) Death receptor 4 (DR4) efficiently kills breast cancer cells irrespective of their sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Gene Therapy 11: 691–698

    CAS  Google Scholar 

  145. Ding X-Z, Adrian TE (2001) Role of lipoxygenase pathways in the regulation of pancreatic cancer cell proliferation and survival. Inflammopharmacology 9: 157–164

    CAS  Google Scholar 

  146. Shureiqi I, Chen D, Lee JJ, Yang P, Newman RA, Brenner DE, Lotan R, Fischer SM, Lippman SM (2000) 15-LOX-1: a novel molecular target of nonsteroidal anti-inflammatory drug-induced apoptosis in colorectal cancer cells. J Natl Cancer Inst 92: 1136–1142

    Article  PubMed  CAS  Google Scholar 

  147. Shureiqi I, Chen D, Lotan R, Yang P, Newman RA, Fischer SM, Lippman SM (2000) 15-lipoxygenase-1 mediates nonsteroidal anti-inflammatory drug-induced apoptosis independenty of cyclooxygenase-2 in colon cancer cells. Cancer Res 60: 6846–6850

    PubMed  CAS  Google Scholar 

  148. Vogt T, McClelland M, Jung B, Popova S, Bogenrieder T, Becker B, Rumpler G (2001) Progression and NSAID-induced apoptosis in malignant melanomas are independent of cyclooxygenase II. Melanoma Res 11: 587–599

    Article  PubMed  CAS  Google Scholar 

  149. He Q, Luo X, Huang Y, Sheikh MS (2002) Apo2L/TRAIL differentially modulates the apoptotic effects of sulindac and a COX-2 selective non-steroidal anti-inflammatory agent in BAX-deficient cells. Oncogene 21: 6032–6040

    PubMed  CAS  Google Scholar 

  150. Harris RE, Beebe-Donk J, Namboodiri KK (2001) Inverse association of non-steroidal anti-inflammatory drugs and malignant melanoma among women. Oncol Rep 8: 655–657

    PubMed  CAS  Google Scholar 

  151. Garcia-Rodriguez LA, Huerta-Alvarez C (2001) Reduced risk of colorectal cancer among long-term users of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs. Epidemiology 12: 88–93

    PubMed  CAS  Google Scholar 

  152. Harris RE, Beebe-Donk J, Schuller HM (2002) Chemoprevention of lung cancer by nonsteroidal anti-inflammatory drugs among cigarette smokers. Oncol Rep 9: 693–695

    PubMed  CAS  Google Scholar 

  153. Harris RE, Chlebowski RT, Jackson RD, Frid DJ, Ascenseo JL, Anderson G, Rodabough RJ, White E, McTiernan A, Women’s Health Initiative (2003) Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women’s Health Initiative. Cancer Res 63: 6096–6101

    PubMed  CAS  Google Scholar 

  154. Okajima E, Denda A, Ozono S, Takahama M, Akai H, Sasaki Y, Kitayama W, Wakabayashi K, Konishi Y (1998) Chemopreventive effects of nimesulide, a selective cyclooxygenase-2 inhibitor, on the development of rat bladder carcinomas initiated by Nbutyl-N-(hydroxybutyl) nitrosamine. Cancer Res 58: 3028–3031

    PubMed  CAS  Google Scholar 

  155. Kitayama W, Denda A, Okajima E, Tsujiuchi T, Konishi Y (1999) Increased expression of cyclooxygenase-2 protein in rat urinary bladder tomors induced by N-butyl-N-(hydroxybutyl) nitrosamine. Carcinogenesis 20: 2305–2310

    Article  PubMed  CAS  Google Scholar 

  156. Fukutake M, Nakatsugi S, Isoi T, Takahashi M, Ohta T, Mamiya S, Taniguchi Y, Sato H, Fukuda K, Sugimura T et al (1998) Suppressive effects of nimesulide, a selective inhibitor of cyclooxygenase-2, on azoxymethane-induced colon carcinogenesis. Carcinogenesis 19: 1939–1942

    Article  PubMed  CAS  Google Scholar 

  157. Nakatsugi S, Ohta T, Kawamori T, Mutoh M, Tanigawa T, Watanabe K, Sugie S, Sugimura T, Wakabayashi K (2000) Chemoprevention by nimesulide, a selective cyclooxygenase-2 inhibitor, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary gland carcinogenesis in rats. Jpn J Cancer Res 91: 886–892

    PubMed  CAS  Google Scholar 

  158. Yoshida K, Tanaka T, Kohno H, Sakata K, Kawamori T, Mori H, Wakabayashi K (2003) A COX-2 inhibitor, nimesulide, inhibits chemically-induced rat tongue carcinogenesis through suppression of cell proliferation activity and COX-2 and iNOS expression. Histol Histopath 18: 39–48

    CAS  Google Scholar 

  159. Hahm KB, Song YJ, Oh TY, Lee JS, Surh YJ, Kim YB, Yoo BM, Kim JH, Han SU, Nahm KT et al (2003) Chemoprevention of Helicobacter pylori-associated gastric carcinogenesis in a mouse model: is it possible? J Biochem Mol Biol 36: 82–94

    PubMed  CAS  Google Scholar 

  160. Furukawa F, Nishikawa A, Lee IS, Kanki K, Umemura T, Okazaki K, Kawamori T, Wakabayashi K, Hirose M (2003) A cycloooxygenase-2 inhibitor, nimesulide, inhibits postinitiation phase of N-nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis in hamsters. Int J Cancer 104: 269–273

    Article  PubMed  CAS  Google Scholar 

  161. Li XH, Li XK, Cai SH, Tang FX, Zhong XY, Ren XD (2003) Synergistic effects of nimesulide and 5-fluorouracil on tumor growth and apoptosis in the implanted hepatoma in mice. World J Gastroenterol 9: 936–940

    PubMed  CAS  Google Scholar 

  162. Li XH, Li JJ, Zhang HW, Sun P, Zhang YL, Cai SH, Ren XD (2003) Nimesulide inhibits tumor growth in mice implanted hepatoma: overexpression of Bax over Bcl-2. Acta Pharmacol Sin 24: 1045–1050

    PubMed  CAS  Google Scholar 

  163. Yamamoto K, Kitayama W, Denda A, Morisaki A, Kuniyasu H, Kirita T (2003) Inhibitory effects of selective cyclooxygenase-2 inhibitors, nimesulidee and etodolac, on the development of squamous cell dysplasias and carcinomas of the tongue in rats initiated with 4-nitroquinoline 1-oxide. Cancer Lett 199: 121–129

    Article  PubMed  CAS  Google Scholar 

  164. Kitamura T, Itoh M, Noda T, Matsuura M, Wakabayashi K (2004) Combined effects of cyclooxygenase-1 and cyclooxygenase-2 selective inhibitors on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice. Int J Cancer 109: 576–580

    Article  PubMed  CAS  Google Scholar 

  165. Nakasugi S, Fukutake M, Takahashi M, Fukuda K, Isoi T, Taniguchi Y, Sugimura T, Wakabayashi K (1997) Suppression of intestinal polyp development by nimesulide, a selective cyclooxygenase-2 inhibitor, in Min mice. Jpn J Cancer Res 88: 1117–1120

    Google Scholar 

  166. Dolara P, Caderni G, Tonelli F (1999) Nimesulide, a selective anti-inflammatory cyclooxygenase-2 inhibitor, does not affect polyp number and mucosal proliferation in familial adenomatous polyposis. Scan J Gastroenterol 34: 1168

    CAS  Google Scholar 

  167. Seed MP, Freemantle CN, Alam CA, Colville-Nash PR, Brown JR, Papworth JL, Somerville KW, Willoughby DA (1997) Apoptosis induction and inhibition of colon-26 timour growth and angiogenesis: findings on COX-1 and COX-2 inhibitors in vitro and in vivo and topical disclofenac in hyaluronan. Adv Exp Med Biol 433: 339–342

    PubMed  CAS  Google Scholar 

  168. Giuliano F, Warner TD (1999) Ex vivo assay to determine the cyclooxygenase selectivity of non-steroidal anti-inflammatory drugs. Br J Pharmacol 126: 1824–1830

    Article  PubMed  CAS  Google Scholar 

  169. Tardieu D, Jaeg JP, Deloly A, Corpet DE, Cadet J, Petit CR (2000) The COX-2 inhibitor nimesulide suppresses superoxide and 8-hydroxy-deoxyguanosine formation, and stimulates apoptosis in mucosa during early colonic inflammation in rats. Carcinogenesis 21: 973–976

    Article  PubMed  CAS  Google Scholar 

  170. Hida T, Kozaki K, Muramatsu H, Masuda A, Shimizu S, Mitsudomi T, Sugiura T, Ogawa M, Takahashi T (2000) Cyclooxygenase-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell cancer cell lines. Clin Cancer Res 6: 2006–2011

    PubMed  CAS  Google Scholar 

  171. Zhang Z, DuBois RN (2000) Par-4, a proaptotic gene, is regulated by NSAIDs in human colon carcinoma cells. Gastroenterology 118: 1012–1017

    Article  PubMed  CAS  Google Scholar 

  172. Godlewski MM, Motyl MA, Gajkowska B, Wareski P, Koronkiewicz M, Motyl T (2001) Subcellular redistribution of BAX during apoptosis induced by anticancer drugs. Anticancer Drugs 12: 607–617

    Article  PubMed  CAS  Google Scholar 

  173. Tian G, Yu JP, Lou HS, Yu BP, Yue H, Li JY, Mei Q (2002) Effect of nimesulide on proliferation and apoptosis of human hepatoma SMMC-7721 cells. World J Gastroenterol 8: 483–487

    PubMed  CAS  Google Scholar 

  174. Lin DT, Subbaramaiah K, Shah JP, Dannenberg AJ, Boyle JO (2002) Cyclooxygenase-2: a novel molecular target for the prevention and treatment of head and neck cancer. Head Neck 24: 792–799

    PubMed  Google Scholar 

  175. Yamazaki R, Kusonoki N, Matsuzaki T, Hashimoto S, Kawai S (2002) Selective cyclooxygenase-2 inhibitors show a differential ability to inhibit proliferation and induce apoptosis of colon adenocarcinoma cells. FEBS Lett 531: 278–284

    Article  PubMed  CAS  Google Scholar 

  176. Godlewski MM, Gajkowski B, Lamparaska-Przybysz M, Motyl T (2002) Colocalization of BAX with BID and VDAC-1 in nimesulide-induced apoptosis of human colon adenocarcinoma COLO 205 cells. Anticancer Drugs 13: 1017–1029

    PubMed  CAS  Google Scholar 

  177. Eibl G, Reber HA, Wente MN, Hines OJ (2003) The selective cyclooxygenase-2 inhibitor nimesulide induces apoptosis in pancreatic cancer cells independent of COX-2. Pancreas 26: 33–41

    Article  PubMed  CAS  Google Scholar 

  178. Pan Y, Zhang JS, Gazi MH, Young CY (2003) The cyclooxygenase 2-specific nonsteroidal anti-inflammatory drugs celecoxib and nimesulide inhibit androgen receptor activity via induction of c-Jun in prostate cells. Cancer Epidemiol Biomarkers Prev 12: 769–774

    PubMed  CAS  Google Scholar 

  179. Totzke G, Schulze-Osthoff K, Janicke RU (2003) Cyclooxygenase-2 (COX-2) inhibitors sensitize tumor cells specifically to death receptor-induced apoptosis independently of COX-2 inhibition. Oncogene 22: 8021–8030

    Article  PubMed  CAS  Google Scholar 

  180. Buecher B, Broquet A, Bouancheau D, Heymann MF, Jany A, Denis MG, Bonnet C, Galmiche JP, Blottiere HM (2003) Molecular mechanisms involved in the antiproliferative effect of two COX-2 inhibitors, nimesulide and NS-398, on colorectal cancer cell lines. Dig Liver Dis 35: 557–565

    Article  PubMed  CAS  Google Scholar 

  181. Chen PY, Long QC (2004) Effects of cyclooxygenase 2 inhibitors on biological traits of nasopharyngeal carcinoma cells. Acta Pharmacol Sin 25: 943–949

    PubMed  CAS  Google Scholar 

  182. Baoping Y, Guoyong H, Jieping Y, Zongxue R, Hesheng L (2004) Cyclooxygenase-2 inhibitor nimesulide suppresses telomerase activity by blocking Akt/PKB activation in gastric cancer cell line. Dig Dis Sci 49: 948–953

    Article  PubMed  Google Scholar 

  183. Okajima E, Uemura H, Ohnishi S, Tanaka M, Ohta M, Tani M, Fujimoto K, Ozono S, Okajima E, Hirao Y (2003) Expression of cyclooxygenase-2 in primary superficial bladder cancer tissue may predict risk of its recurrence after complete transurethral resection. Aktuelle Urol 34: 256–258

    PubMed  CAS  Google Scholar 

  184. Li JY, Wang XZ, Chen FL, Yu JP, Luo HS (2003) Nimesulide inhibits proliferation via induction of apoptosis and cell cycle arrest in human gastric carcinoma cell line. World J Gastroenterol 9: 915–920

    PubMed  CAS  Google Scholar 

  185. Eibl G, Bruemmer D, Okada Y, Duffy JP, Law RE, Reber HA, Hines OJ (2003) PGE2 is generated by a specific COX-2 activity and increases VEGF production in COX-2-expressing human pancreatic cancer cells. Biochem Biophys Res Commun 306: 887–897

    Article  PubMed  CAS  Google Scholar 

  186. Haynes A, Shaik MS, Chatterjee A, Singh M (2003) Evaluation of an aerosolized selective COX-2 inhibitor as a potentiator of doxorubicin in non-small-cell lung cancer cell line. Pharm Res 20: 1485–1495

    Article  PubMed  CAS  Google Scholar 

  187. Xing L, Zhang Z, Xu Y, Zhang H, Liu J (2004) The effects of nimesulide combined with cisplatin on lung cancer. J Huazhong Univ Sci Technolog Med Sci 24: 120–123

    PubMed  CAS  Google Scholar 

  188. Makowski M, Grzela T, Niderla J, Lazarczyk M, Mroz P, Kopee M, Legat M, Strusinska K, Koziak K, Nowis D et al. (2003) Inhibition of cyclooxygenase-2 indirectly potentiates antitumor effects of photodynamic therapy in mice. Clin Cancer Res 9: 5419–5422

    Google Scholar 

  189. Akita Y, Kozaki K, Nakagawa A, Saito T, Ito S, Tamada Y, Fujiwara S, Nishikawa N, Uchida K, Yoshikawa K et al (2004) Cyclooxygenase-2 is a possible target of treatment approach in conjunction with photodynamic therapy for various disorders in skin and oral cavity. Br J Dermatol 151: 472–480

    Article  PubMed  CAS  Google Scholar 

  190. Selko DJ (1994) Amyloid beta-protein precursor: new clues to the genesis of Alzheimer’s disease. Curr Opin Neurobiol 4: 708–716

    Google Scholar 

  191. Tuppo EE, Arias HR (2005) The role of inflammation in Alzheimer’s disease. Int J Biochem Cell Biol 37: 289–305

    Article  PubMed  CAS  Google Scholar 

  192. Breitner JCS, Welsh KA, Helms MJ, Gaskell PC, Gau BA, Roses AD, Pericakvance MA (1995) Delayed onset of Alzheimer’s disease with nonsteroidal anti-inflammatory and histamine H2 drugs. Neurobiology of Aging 16: 523–530

    Article  PubMed  CAS  Google Scholar 

  193. Andersen K, Launer LJ, Ott A, Hoes AW, Breteler MMB, Hofman A (1995) Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer’s disease? The Rotterdam Study. Neurology 45: 1441–1445

    PubMed  CAS  Google Scholar 

  194. McGeer PL, Schulzer M, McGeer EG (1996) Arthritis and anti-inflammatory agents as possible protective factors for Alzeimer’s disease: a review of 17 epidemiological studies. Neurology 47: 425–432

    PubMed  CAS  Google Scholar 

  195. Etminan M, Gill S, Samii A (2003) Effect of non-steroidal anti-inflammatory drug on risk of Alzheimer’s disease: systematic review and meta-analysis of observational studies. Br Med J 327: 128

    CAS  Google Scholar 

  196. Szekely CA, Thorne JE, Zandi PP, Ek M, Messias E, Breitner JC, Goodman SN (2004) Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer’s disease: a systematic review. Neuroepidemiology 23: 159–169

    Article  PubMed  Google Scholar 

  197. Stewart WF, Kawas C, Corrada M, Metter EJ (1997) Risk of Alzheimer’s disease and duration of NSAID use. Neurology 48: 626–632

    PubMed  CAS  Google Scholar 

  198. Scharf S, Mander A, Ugoni A, Vajda F, Christophidis N (1999) A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer’s disease. Neurology 53: 197–201

    PubMed  CAS  Google Scholar 

  199. Lopez-Pousa S, Mercadal-Dalmau J, Marti-Cuadros AM, Vilalta-Franch J, Lozano-Gallego M (1997) Triflusal in the prevention of vascular dementia. Rev Neurol 25: 1525–1528 (in Spanish)

    PubMed  CAS  Google Scholar 

  200. Aisen PS, Schmeidler J, Pasinetti GM (2002) Randomized pilot study of nimesulide treatment of Alzheimer’s disease. Neurology 58: 1050–1054

    PubMed  CAS  Google Scholar 

  201. Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL, Farlow MR, Jin S, Thomas RG, Thal LJ; Alzheimer’s Disease Cooperative Study (2003) Effects of rofecoxib or naproxen vs placebo on Alzheimer’s disease progression: a randomized controlled trial. J Am Med Assoc 289: 2819–2826

    Article  CAS  Google Scholar 

  202. Reines SA, Block GA, Morris JC, Liu G, Nessly ML, Lines CR, Norman BA, Baranak CC; Rofecoxib Protocol 091 Study Group (2004) Rofecoxib: no effect on Alzheimer’s disease in a 1-year, randomized, blinded, controlled study. Neurology 62: 66–71

    PubMed  CAS  Google Scholar 

  203. Avramovich Y, Amit T, Youdim MBH (2002) Non-steroidal anti-inflammatory drugs stimulate secretion of non-amyloidogenic precursor protein. J Biol Chem 277: 31466–31473

    Article  PubMed  CAS  Google Scholar 

  204. Koyfman L, Kaplanski J, Artru AA, Talmor D, Rubin M, Shapira Y (2000) Inhibition of cyclooxygenase 2 by nimesulide decreases prostaglandin E2 formation but does not alter brain edema or clinical recovery after closed head injury in rats. J Neurosurg Anesthesiol 12: 44–50

    PubMed  CAS  Google Scholar 

  205. Cernak I, O’Connor C, Vink R (2002) Inhibition of cyclooxygenase 2 by nimesulide improves cognitive outcome more than motor outcome following diffuse traumatic injury in rats. Exp Brain Res 147: 193–199

    Article  PubMed  CAS  Google Scholar 

  206. Cernak I, O’Connor C, Vink R (2001) Activation of cyclo-oxygenase-2 contributes to motor and cognitive dysfunction following diffuse traumatic brain injury in rats. Clin Exp Pharmacol Physiol 28: 922–925

    Article  PubMed  CAS  Google Scholar 

  207. Naidu PS, Kulkarni SK (2002) Differential effects of cyclooxygenase inhibitors on haloperidol-induced catalepsy. Prog Neuropsychopharmacol Biol Psychiatry 26: 819–822

    Article  PubMed  CAS  Google Scholar 

  208. Le Filliatre G, Sayah S, Latournerie V, Renaud JF, Finet M, Hanf R (2001) Cyclo-oxygenase and lipoxygenase pathways in mast cell dependent-neurogenic inflammation induced by electrical stimulation of the rat saphenous nerve. Br J Pharmacol 132: 1581–1589

    PubMed  Google Scholar 

  209. Shemi D, Azab AN, Kaplanski J (2000) Time-dependent effect of LPS on PGE2 and TNF-alpha production by rat glial brain culture: influence of COX and cytokine inhibitors. J Endotoxin Res 6: 377–381

    Article  PubMed  CAS  Google Scholar 

  210. Jain NK, Kulkarni SK, Singh A (2001) Lipopolysaccharide-mediated immobility in mice: reversal by cyclooxygenase enzyme inhibitors. Methods Find Exp Clin Pharmacol 23: 441–444

    Article  PubMed  CAS  Google Scholar 

  211. Boje KM, Jaworowicz D Jr, Raybon JJ (2003) Neuroinflammatory role of prostaglandins during experimental meningitis: evidence suggestive of an in vivo relationship between nitric oxide and prostaglndins. J Pharmacol Exp Ther 304: 319–325

    Article  PubMed  CAS  Google Scholar 

  212. Spielman L, Winger D, Ho L, Aisen PS, Shoharmi E, Pasinetti GM (2002) Induction of the complement component ClB in brain of transgenic mice with neuronal overexpression of human cyclooxygenase-2. Acta Neuropathol 103: 157–162

    Article  PubMed  CAS  Google Scholar 

  213. Mirjany M, Ho L, Pasinetti GM (2002) Role of cyclooxygenase-2 in neuronal cell cycle activity ad glutamate-mediated excitotoxicity. J Pharmacol Exp Ther 301: 494–500

    Article  PubMed  CAS  Google Scholar 

  214. Jain NK, Patil CS, Kulkarni SK, Singh A (2002) Modulatory role of cyclooxygenase inhibitors in aging-and scopolamine or lipopolysaccharide-induced cognitive dysfunction in mice. Behav Brain Res 133: 369–376

    Article  PubMed  CAS  Google Scholar 

  215. Fattore L, Melis M, Diana M, Fratt W, Gessa G (2000) The cyclo-oxygenase inhibitor nimesulide induces conditioned place preference in rats. Eur J Pharmacol 406: 75–77

    Article  PubMed  CAS  Google Scholar 

  216. Kunz T, Oliw EH (2001) Nimesulide aggravates kainic acid-induced seizures in the rat. Pharmacol Toxicol 88: 271–276

    PubMed  CAS  Google Scholar 

  217. Candelario-Jalil E, Ajamieh HH, Sam S, Martinez G, Leon Fernandez OS (2000) Nimesulide limits kainate-induced oxidative damage in the rat hippocampus. Eur J Pharmacol 390: 295–298

    Article  PubMed  CAS  Google Scholar 

  218. Chen C, Magee JC, Bazan NG (2002) Cyclooxygenase-2 regulates prostaglandin E2 signaling in hippocampal long-term synaptic plasticity. J Neurophysiol 87: 2851–2857

    PubMed  CAS  Google Scholar 

  219. Grilli M, Pizzi M, Memo M, Spano P (1997) Use of selected nonsteroidal antiinflammatory compounds for the prevention and the treatment of neurodegenerative diseases. Patent No. WO 9820864

    Google Scholar 

  220. Pasinetti GM, Aisen PS (2004) Treatment of neurodegenerative conditions with nimesulide. Patent No. WO 9822104

    Google Scholar 

  221. Aisen PS, Pasinetti GM (1999) Treatment of neurodegenerative conditions with nimesulide. Patent No. US19970831402

    Google Scholar 

  222. Koo EHM, Golde TE, Galsko DR (2001) Nonsteroidal antiinflammatory dug (NSAID) and NSAID derivative Alzheimer’s. Patent No. WO 2001078721

    Google Scholar 

  223. Aisen P, Pasinetti GM (2000) Treating of neurodegenerative conditions use of nimesulide for the preparation of pharmaceutical compositions. Patent No. HU 9904544

    Google Scholar 

  224. Pasinetti GM (2003) Inhibiting progressive cognitive impairment. Patent No. WO 2003105820

    Google Scholar 

  225. Isakson PC (2004) Monotherapy for the treatment of amyotrophic lateral sclerosis with cyclooxygenase-2 (COX-2) inhibitor(s). Patent No. WO 2003101441

    Google Scholar 

  226. Slattery MM, Friel AM, Healy DG, Morrison JJ (2001) Uterine relaxant effects of cyclooxygenase-2 inhibitors in vitro. Obstet Gynecol 98: 563–569

    Article  PubMed  CAS  Google Scholar 

  227. Grigsby PL, Poore KR, Hirst JJ, Jenkin G (2000) Inhibition of premature labor in sheep by a combined treatment of nimesulide. A prostaglandin synthase type 2 inhibitor, and atosiban, an oxytocin receptor antagonist. Am J Obstet Gynecol 183: 649–657

    Article  PubMed  CAS  Google Scholar 

  228. Scott JE, Grigsby PL, Hirst JJ, Jenkin G (2001) Inhibition of prostaglandin synthesis and its effect on uterine activity during established premature labor in sheep. J Soc Gynecol Investig 8: 266–276

    Article  PubMed  CAS  Google Scholar 

  229. Locatelli A, Vergani P, Bellini P, Strobelt N, Ghidini A (2001) Can a cyclo-oxygenase type-2 selective tocolytic agent avoid the fetal side effects of indomethacin? BJOG 108: 325–326

    Article  PubMed  CAS  Google Scholar 

  230. Holmes RP, Stone PR (2000) Severe oligohydramnios induced by cyclooxygenase-2 inhibitor nimesulide. Obstet Gynecol 96(5 Pt 2): 810–811

    PubMed  CAS  Google Scholar 

  231. Sawdy RJ, Lye S, Fisk NM, Bennett PR (2003) A double-blind randomized study of fetal side effects during and after the short-term maternal administration of indomethacin, sulindac, and nimesulide for the treatment of preterm labor. Am J Obstet Gynecol 188: 1046–1051

    Article  PubMed  CAS  Google Scholar 

  232. Bennett PR (2004) Cyclooxygenase-2 (COX-2) selective inhibitors for managing labour and uterine contractions. Patent No. WO 9731631

    Google Scholar 

  233. Rahmouni-Piette S, Mutschen M, Aukurst PAL, Johansson C, Hansson V, Tasken K, Froeland SS, Klaveness J, Aandahl EM (2003) Use of COX-2 inhibitors for preventing immunodeficiency. Patent No. US2004082640

    Google Scholar 

  234. Rodriguez-Soriano J (1999) Bartter’s syndrome comes of age. Pediatrics 103(3): 663–664

    Article  PubMed  CAS  Google Scholar 

  235. Nusing RM, Reinalter SC, Peters M, Komhoff M, Seyberth HW (2001) Pathogenetic role of cyclooxygenase-2 in hyperprostaglandin E syndrome/antenatal Bartter syndrome: therapeutic use of the cyclooxygenase-2 inhibitor nimesulide. Clin Pharmacol Ther 70: 384–390

    PubMed  CAS  Google Scholar 

  236. Reinalter SC, Jeck N, Brochhausen C, Watzer B, Nusing RM, Seyberth HW, Komhoff M (2002) Role of cyclooxygenase-2 in hyperprostaglandin E syndrome/antenatal Bartter syndrome. Kidney Int 62: 253–260

    Article  PubMed  CAS  Google Scholar 

  237. Filippo D (1992) The use of nimesulide in the treatment of cataract. Patent No. EP0532900

    Google Scholar 

  238. Matsuo K, Hojou H, Honbou M, Miyata N (1995) Clinical efficacy of diclofenac sodium on postsurgical inflammation after intraocular lens implantation. J Cataract Refract Surg 21: 309–312

    PubMed  CAS  Google Scholar 

  239. Italian Diclofenac Study Group. Efficacy of diclofenac eyedrops in preventing postoperative inflammation and long-term cystoid macular edema. Br J Cataract Refract Surg 23: 183–189

    Google Scholar 

  240. Gupta SK, Joshi S, Tandon R, Mathur P (1997) Topical aspirin provides protection against galactosemic cataract. Indian J Ophthalmol 45: 221–225

    PubMed  CAS  Google Scholar 

  241. Christen WG, Manson JE, Glynn RJ, Ajani UA, Schaumberg DA, Sperduto RD, Buring JE, Hennekens CH (1998) Low-dose aspirin and risk of cataract and subtypes in a randomized trial of US physicians. Ophthalmic Epidemiol 5: 133–142

    Article  PubMed  CAS  Google Scholar 

  242. Gaynes BI, Fiscella R (2002) Topical nonsteroidal anti-inflammatory drugs for ophthalmic use: a safety review. Drug Saf 25: 233–250

    PubMed  CAS  Google Scholar 

  243. Schalnus R (2003) Topical nonsteroidal anti-inflammatory therapy in ophthalmology. Ophthalmlogica 217: 89–98

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Birkäuser Verlag Basel/Switzerland

About this chapter

Cite this chapter

Rainsford, K. (2005). The discovery, development and novel actions of nimesulide. In: Rainsford, K. (eds) Nimesulide — Actions and Uses. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7410-1_1

Download citation

Publish with us

Policies and ethics