DP-155, a lecithin derivative of indomethacin, is a novel nonsteroidal antiinflammatory drug for analgesia and Alzheimer's disease therapy

CNS Drug Reviews

Volumn 13, Issue 2, 2007, Pages 260-277

  Dvir, Eran ^a,e   Elman, Anat ^b   Simmons, Danielle ^c   Shapiro, Israel ^a   Duvdevani, Revital ^a   Dahan, Arik ^d   Hoffman, Amnon ^d   Friedman, Jonathan E ^a  

^a D Pharm Ltd   (Israel)

^b VOLCANI CENTER   (Israel)

^c Thuris Corporation   (United States)

^d HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^e UNIVERSITY OF PRETORIA   (South Africa)

Author keywords

Gastrointestinal; Phospholipid; Prodrug; Renal; Toxicity

Indexed keywords

CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; DP 155; INDOMETACIN; NONSTEROID ANTIINFLAMMATORY AGENT; PHOSPHATIDYLCHOLINE; PHOSPHOLIPASE A2; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANTIPYRETIC ACTIVITY; BLOOD; BRAIN LEVEL; DRUG EFFICACY; DRUG HALF LIFE; DRUG INHIBITION; DRUG SAFETY; DRUG SYNTHESIS; ENZYME ACTIVITY; GASTROINTESTINAL TOXICITY; HUMAN; IN VITRO STUDY; IN VIVO STUDY; NEPHROTOXICITY; NERVE DEGENERATION; NONHUMAN; REVIEW; RHEUMATOID ARTHRITIS;

ALZHEIMER DISEASE; ANALGESICS; ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; CYCLOOXYGENASE 2; DRUG COMBINATIONS; HUMANS; INDOMETHACIN; PHOSPHATIDYLCHOLINES; PHOSPHOLIPASES A; RATS;

EID: 34447323271     PISSN: 1080563X     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1527-3458.2007.00014.x     Document Type: Review

References (63)

1. Agdeppa ED, Kepe V, Petri A, Satyamurthy N, Liu J, Huang SC, Small GW, Cole GM, Barrio JR (2003) In vitro detection of (S)-naproxen and ibuprofen binding to plaques in the Alzheimer's brain using the positron emission tomography molecular imaging probe 2-(1-[6-[(2-[(18)F]fluoroethyl)(methyl)amino] -2-naphthyl]ethylidene)malono nitrile. Neuroscience 117 : 723 730.
2. Arnold L, Collins C, Starmer GA (1974) Renal and gastric lesions after phenylbutazone and indomethacin in the rat. Pathology 6 : 303 313.
3. Ayano Y, Yamasaki K, Soejima H, Ikegami K (1984) Role of the renal prostaglandins in furosemide-induced diuresis. Urol Int 39 : 25 28.
4. Bi X, Gall CM, Zhou J, Lynch G (2002) Uptake and pathogenic effects of amyloid beta peptide 1-42 are enhanced by integrin antagonists and blocked by NMDA receptor antagonists. Neuroscience 112 : 827 840.
5. Chapman PF, White GL, Jones MW, Cooper-Blacketer D, Marshall VJ, Irizarry M, Younkin L, Good MA, Bliss TV, Hyman BT, et al 1999) Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nat Neurosci 2 : 271 276.
6. Citron M, Vigo-Pelfrey C, Teplow DB, Miller C, Schenk D, Johnston J, Winblad B, Venizelos N, Lannfelt L, Selkoe DJ (1994) Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation. Proc Natl Acad Sci USA 91 : 11993 11997.
7. Clark WG, Cumby HR (1975) The antipyretic effect of indomethacin. J Physiol 248 : 625 638.
8. Colangelo V, Schurr J, Ball MJ, Pelaez RP, Bazan NG, Lukiw WJ (2002) Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: Transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling. J Neurosci Res 70 : 462 473.
9. D'Andrea MR, Nagele RG, Wang HY, Peterson PA, Lee DH (2001) Evidence that neurones accumulating amyloid can undergo lysis to form amyloid plaques in Alzheimer's disease. Histopathology 38 : 120 134.
10. Dahan A, Duvdevani R, Dvir E, Elmann A, Hoffman A (2007) A novel mechanism for oral controlled release of drugs by continuous degradation of a phospholipid prodrug along the intestine: In-vivo and in-vitro evaluation of an indomethacin-lecithin conjugate. J Control Release 119 : 86 93.
11. De Souza GE, Cardoso RA, Melo MC, Fabricio AS, Silva VM, Lora M, De Brum-Fernandes AJ, Rae GA, Ferreira SH, Zampronio AR (2002) A comparative study of the antipyretic effects of indomethacin and dipyrone in rats. Inflamm Res 51 : 24 32.
12. DeLeo JA, Colburn RW, Coombs DW, Ellis MA (1989) The differentiation of NSAIDs and prostaglandin action using a mechanical visceral pain model in the rat. Pharmacol Biochem Behav 33 : 253 255.
13. Dormond O, Foletti A, Paroz C, Ruegg C (2001) NSAIDs inhibit alpha V beta 3 integrin-mediated and Cdc42/Rac-dependent endothelial-cell spreading, migration and angiogenesis. Nat Med 7 : 1041 1047.
14. Dvir E, Friedman JE, Lee JY, Koh JY, Younis F, Raz S, Shapiro I, Hoffman A, Dahan A, Rosenberg G, et al 2006) A novel phospholipid derivative of indomethacin, DP-155 [mixture of 1-steroyl and 1-palmitoyl-2-{6-[1-(p- chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl acetamido]hexanoyl}-sn-glycero-3- phosophatidyl [corrected] choline], shows superior safety and similar efficacy in reducing brain amyloid beta in an Alzheimer's disease model. J Pharmacol Exp Ther 318 : 1248 1256.
15. Eriksen JL, Sagi SA, Smith TE, Weggen S, Das P, McLendon DC, Ozols VV, Jessing KW, Zavitz KH, Koo EH et al 2003) NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. J Clin Invest 112 : 440 449.
16. Fries JF, Singh G, Ramey DR (1998) The clinical epidemiology of non-steroidal anti-inflammatory drug gastropathy, in Clinical Significance and Potential of Selective COX-2 Inhibitors (Vane J and Botting R eds) pp 57 65, William Harvey Press, London.
17. Garcia-Vicuna R, Diaz-Gonzalez F, Gonzalez-Alvaro I, del Pozo MA, Mollinedo F, Cabanas C, Gonzalez-Amaro R, Sanchez-Madrid F (1997) Prevention of cytokine-induced changes in leukocyte adhesion receptors by nonsteroidal antiinflammatory drugs from the oxicam family. Arthritis Rheum 40 : 143 153.
18. Gasparini L, Ongini E, Wenk G (2004) Non-steroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease: Old and new mechanisms of action. J Neurochem 91 : 521 536.
19. Giraud MN, Motta C, Romero JJ, Bommelaer G, Lichtenberger LM (1999) Interaction of indomethacin and naproxen with gastric surface-active phospholipids: A possible mechanism for the gastric toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs). Biochem Pharmacol 57 : 247 254.
20. Gouras GK, Tsai J, Naslund J, Vincent B, Edgar M, Checler F, Greenfield JP, Haroutunian V, Buxbaum JD, Xu H, et al 2000) Intraneuronal Abeta42 accumulation in human brain. Am J Pathol 156 : 15 20.
21. Halliday G, Robinson SR, Shepherd C, Kril J (2000a) Alzheimer's disease and inflammation: A review of cellular and therapeutic mechanisms. Clin Exp Pharmacol Physiol 27 : 1 8.
22. Halliday GM, Shepherd CE, McCann H, Reid WG, Grayson DA, Broe GA, Kril JJ (2000b) Effect of anti-inflammatory medications on neuropathological findings in Alzheimer disease. Arch Neurol 57 : 831 836.
23. Holcomb L, Gordon MN, McGowan E, Yu X, Benkovic S, Jantzen P, Wright K, Saad I, Mueller R, Morgan D, et al 1998) Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat Med 4 : 97 100.
24. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G (1996) Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274 : 99 102.
25. Hu XH, Tang HW, Li QS, Huang XF (1994) Central mechanism of indomethacin analgesia. Eur J Pharmacol 263 : 53 57.
26. Ivanov IT, Tzaneva M (2002) Direct cytotoxicity of non-steroidal anti-inflammatory drugs in acidic media: Model study on human erythrocytes with DIDS-inhibited anion exchanger. Pharmazie 57 : 848 851.
27. Jurna I, Brune K (1990) Central effect of the non-steroid anti-inflammatory agents, indomethacin, ibuprofen, and diclofenac, determined in C fibre-evoked activity in single neurones of the rat thalamus. Pain 41 : 71 80.
28. Kawarabayashi T, Younkin LH, Saido TC, Shoji M, Ashe KH, Younkin SG (2001) Age-dependent changes in brain, CSF, and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer's disease. J Neurosci 21 : 372 381.
29. Kudo I, Murakami M (2002) Phospholipase A2 enzymes. Prostaglandins Other Lipid Mediat 68-69 : 3 58.
30. Kurz M, Scriba GK (2000) Drug-phospholipid conjugates as potential prodrugs: Synthesis, characterization, and degradation by pancreatic phospholipase A(2). Chem Phys Lipids 107 : 143 157.
31. Lambert DM (2000) Rationale and applications of lipids as prodrug carriers. Eur J Pharm Sci 11 (Suppl 2) : S15 27.
32. Leyck S, Dereu N, Etschenberg E, Ghyczy M, Graf E, Winkelmann J, Parnham MJ (1985) Improvement of the gastric tolerance of non-steroidal anti-inflammatory drugs by polyene phosphatidylcholine (Phospholipon 100). Eur J Pharmacol 117 : 35 42.
33. Lin B, Arai AC, Lynch G, Gall CM (2003) Integrins regulate NMDA receptor-mediated synaptic currents. J Neurophysiol 89 : 2874 2878.
34. MacDonald TM (2000) Epidemiology and pharmacoeconomic implications of non-steroidal anti-inflammatory drug-associated gastrointestinal toxicity. Rheumatology (Oxford) 39 (Suppl 2) : 13 20 discussion 57-19.
35. Markus HS, Vallance P, Brown MM (1994) Differential effect of three cyclooxygenase inhibitors on human cerebral blood flow velocity and carbon dioxide reactivity. Stroke 25 : 1760 1764.
36. McCulloch J, Kelly PA, Grome JJ, Pickard JD (1982) Local cerebral circulatory and metabolic effects of indomethacin. Am J Physiol 243 : H416 H423.
37. McGeer PL, McGeer EG (1999) Inflammation of the brain in Alzheimer's disease: Implications for therapy. J Leukoc Biol 65 : 409 415.
38. McGeer PL, McGeer EG (2007) NSAIDs and Alzheimer disease: Epidemiological, animal model and clinical studies. Neurobiol Aging 28 : 639 647.
39. McMahon SB (1997) Are there fundamental differences in the peripheral mechanisms of visceral and somatic pain? Behav Brain Sci 20 : 381 391 discussion 435-513.
40. Moechars D, Dewachter I, Lorent K, Reverse D, Baekelandt V, Naidu A, Tesseur I, Spittaels K, Haute CV, Checler et al 1999) Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain. J Biol Chem 274 : 6483 6492.
41. Pratico D, Uryu K, Leight S, Trojanoswki JQ, Lee VM (2001) Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J Neurosci 21 : 4183 4187.
42. Psaty BM, Furberg CD (2005) COX-2 inhibitors - lessons in drug safety. N Engl J Med 352 : 1133 1135.
43. Roberts LJI, Morrow JD (2001) Analgesic-antipyretic and anitiinflammatory agents and drugs employed in the treatment of gout, in Goodman & Gilman's The Pharmacological Basis of Therapeutics (Hardman JG, Limbird LE and Gilman AG eds) pp 687 731, McGraw-Hill, New York.
44. Rogers J, Kirby LC, Hempelman SR, Berry DL, McGeer PL, Kaszniak AW, Zalinski J, Cofield M, Mansukhani L, Willson P et al. (1993) Clinical trial of indomethacin in Alzheimer's disease. Neurology 43 : 1609 1611.
45. Rogers J, Webster S, Lue LF, Brachova L, Civin WH, Emmerling M, Shivers B, Walker D, McGeer P (1996) Inflammation and Alzheimer's disease pathogenesis. Neurobiol Aging 17 : 681 686.
46. Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, Bird TD, Hardy J, Hutton M, Kukull W, et al 1996) Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nat Med 2 : 864 870.
47. Schwab JM, Schluesener HJ, Meyermann R, Serhan CN (2003) COX-3 the enzyme and the concept: Steps towards highly specialized pathways and precision therapeutics? Prostaglandins Leukot Essent Fatty Acids 69 : 339 343.
48. Stephenson DT, Lemere CA, Selkoe DJ, Clemens JA (1996) Cytosolic phospholipase A2 (cPLA2) immunoreactivity is elevated in Alzheimer's disease brain. Neurobiol Dis 3 : 51 63.
49. Stichtenoth DO, Frölich JC (1998) Avoidance of renal side effects of non-steroidal anti-inflammatory drugs: Value of selective cyclooxygenase-2 inhibition, in Clinical Significance and Potential of Selective COX-2 Inhibitors (Vane J and Botting R eds) pp 99 108, William Harvey Press, London.
50. Sung S, Yang H, Uryu K, Lee EB, Zhao L, Shineman D, Trojanowski JQ, Lee VM, Pratico D (2004) Modulation of nuclear factor-kappa B activity by indomethacin influences A beta levels but not A beta precursor protein metabolism in a model of Alzheimer's disease. Am J Pathol 165 : 2197 2206.
51. Tabet N, Feldman H (2002) Indomethacin for the treatment of Alzheimer's disease patients. Cochrane Database Syst Rev : CD003673.
52. Takahashi RH, Milner TA, Li F, Nam EE, Edgar MA, Yamaguchi H, Beal MF, Xu H, Greengard P, Gouras GK (2002) Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am J Pathol 161 : 1869 1879.
53. Thomas T, Nadackal TG, Thomas K (2001) Aspirin and non-steroidal anti-inflammatory drugs inhibit amyloid-beta aggregation. Neuroreport 12 : 3263 3267.
54. t' Veld BA, Ruitenberg A, Hofman A, Launer LJ, van Duijn CM, Stijnen T, Breteler MM, Stricker BH (2001) Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. N Engl J Med 345 : 1515 1521.
55. Vogel HG, Vogel WH (1997) Drug Discovery and Evaluation Pharmcological Assays. Springer, Berlin.
56. Weggen S, Eriksen JL, Das P, Sagi SA, Wang R, Pietrzik CU, Findlay KA, Smith TE, Murphy MP, Bulter T, et al 2001) A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature 414 : 212 216.
57. Weggen S, Eriksen JL, Sagi SA, Pietrzik CU, Ozols V, Fauq A, Golde TE, Koo EH (2003) Evidence that nonsteroidal anti-inflammatory drugs decrease amyloid beta 42 production by direct modulation of gamma-secretase activity. J Biol Chem 278 : 31831 31837.
58. Weyant MJ, Carothers AM, Bertagnolli ME, Bertagnolli MM (2000) Colon cancer chemopreventive drugs modulate integrin-mediated signaling pathways. Clin Cancer Res 6 : 949 956.
59. Whittle BJR (1998) Experimental basis for non-steroidal anti-inflammatory drug-induced gut injury, in Clinical Significance and Potential of Selective COX-2 Inhibitors (Vane J and Botting R eds) pp 67 76, William Harvey Press, London.
60. Willoughby DA, Moore AR, Colville-Nash PR (2000) COX-1, COX-2, and COX-3 and the future treatment of chronic inflammatory disease. Lancet 355 : 646 648.
61. Wirths O, Multhaup G, Czech C, Blanchard V, Moussaoui S, Tremp G, Pradier L, Beyreuther K, Bayer TA (2001) Intraneuronal Abeta accumulation precedes plaque formation in beta-amyloid precursor protein and presenilin-1 double-transgenic mice. Neurosci Lett 306 : 116 120.
62. Yazawa K, Tsuno NH, Kitayama J, Kawai K, Okaji Y, Asakage M, Sunami E, Kaisaki S, Hori N, Watanabe T, et al 2005) Selective inhibition of cyclooxygenase-2 inhibits colon cancer cell adhesion to extracellular matrix by decreased expression of beta1 integrin. Cancer Sci 96 : 93 99.
63. Zipp F, Aktas O (2006) The brain as a target of inflammation: Common pathways link inflammatory and neurodegenerative diseases. Trends Neurosci 29 : 518 527.