Nitrone spin on cerebral ischemia

Current Opinion in Investigational Drugs

Volumn 7, Issue 1, 2006, Pages 20-24

  Doggrell, Sheila A ^a  

^a AUCKLAND UNIVERSITY OF TECHNOLOGY   (New Zealand)

Author keywords

Animal model; Azulenyl nitrone; Cerebral ischemia; Clinical trial; NXY 059; PBN; S PBN; Stilbazulenyl nitrone

Indexed keywords

1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; 3 NITROPROPIONIC ACID; 3,4 DIHYDRO 3,3 DIMETHYLISOQUINOLINE 2 OXIDE; ANTIOXIDANT; AZULENYLNITRONE DERIVATIVE; CLOMETHIAZOLE; CREATININE; CYTOCHROME C; DISUFENTON SODIUM; DOPAMINE; FIBRINOLYTIC AGENT; GUAIAZULENE; LANICEMINE; MALONALDEHYDE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; N TERT BUTYL (2 SULFOPHENYL) NITRONE; N TERT BUTYL ALPHA PHENYLNITRONE; NITRONE DERIVATIVE; PLACEBO; S 34176; SCAVENGER; STILBAZULENYLNITRONE; TENECTEPLASE; TISSUE PLASMINOGEN ACTIVATOR; UNCLASSIFIED DRUG;

BARTHEL INDEX; BRAIN INFARCTION; BRAIN INJURY; BRAIN ISCHEMIA; CEREBROVASCULAR ACCIDENT; CLINICAL TRIAL; DRUG BLOOD LEVEL; DRUG DOSE REGIMEN; DRUG HALF LIFE; DRUG PENETRATION; DRUG POTENCY; DRUG STRUCTURE; HUMAN; HUNTINGTON CHOREA; MIDDLE CEREBRAL ARTERY OCCLUSION; NEUROPROTECTION; NONHUMAN; OSMOTIC MINIPUMP; PARKINSON DISEASE; REVIEW; SPIN TRAPPING; STROKE; TREATMENT FAILURE; VITAMIN SUPPLEMENTATION;

ANIMALS; BRAIN ISCHEMIA; CLINICAL TRIALS; HUMANS; MOLECULAR STRUCTURE; NITROGEN OXIDES; TREATMENT OUTCOME;

EID: 30944433361     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (40)

1. Mohr JP, Gauther JC, Hier D, Stein RW: Middle cerebral artery. In: Stroke: Pathophysiology, Diagnosis and Management. Barnett HJ, Mohr JP, Stein BM, Yatsu FM (Eds), Churchill Livingstone, New York, NY, USA (1992) 1:377-450.
2. Ringelstein EB, Biniek R, Wehller C, Ammeling B, Nolte PN, Thron A: Type and extent of hemispheric brain infarctions and clinical outcome in early and delayed middle cerebral artery recanalization. Neurology (1992) 42(2):289-298.
3. Sanchez-Moreno C, Dashe JF, Scott T, Thaler D, Folstein MF, Martin A: Decreased levels of plasma vitamin C and increased concentration of inflammatory and oxidative stress markers after stroke. Stroke (2004) 35(1):163-168.
4. Heart Protection Study Collaborative Group: MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: A randomised placebo-controlled trial. Lancet (2002) 360(9326):23-33.
5. Green AR, Ashwood T: Free radical trapping as a therapeutic approach to neuroprotection in stroke: Experimental and clinical studies with NXY-059 and free radical scavengers. Curr Drug Targets CNS Neurol Disord (2005) 4(2):109-118.
6. Phillis JW, Clough-Helfman C: Protection from cerebral ischemic injury in gerbils with the spin trap agent N-tert-butyl-α-phenylnitrone (PBN). Neurosci Lett (1990) 116(3):315-319.
7. Clough-Helfman C, Phillis JW: The free radical trapping agent N-tert-butyl-α-phenylnitrone (PBN) attenuates cerebral ischaemic injury in gerbils. Free Radic Res Commun (1991) 15(3):177-186.
8. Sen S, Phillis JW: α-Phenyl-tert-butyl-nitrone (PBN) attenuated hydroxyl radical production during ischemia-reperfusion injury of rat brain: An EPR study. Free Radic Res Commun (1993) 19(4):255-265.
9. Zausinger S, Hungerhuber E, Baethmann A, Reulen H, Schmid-Elsaesser R: Neurological impairment in rats after transient middle cerebral artery occlusion: A comparative study under various treatment paradigms. Brain Res (2000) 863(1-2):94-105.
10. Yang Y, Li Q, Shuaib A: Neuroprotection by 2-h postischemia administration of two free radical scavengers, α-phenyl-N-tert-butyl-nitrone (PBN) and N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN), in rats subjected to focal embolic cerebral ischemia. Exp Neurol (2000) 163(1):39-45.
11. Thomas CF, Ohlweiler DF, Carr AA, Nieduzak TR, Hay DA, Adams G, Vaz R, Bernotas RC: Characterization of the radical trapping activity of a novel series of cyclic nitrone spin traps. J Biol Chem (1996) 271(6):3097-3104.
12. Johnson MP, McCarty DR, Velayo NL, Markgraf CG, Chmielewski PA, Ficorilli JV, Cheng HC, Thomas CE: MDL 101,002, a free radical spin trap, is efficacious in permanent and transient focal ischemia models. Life Sci (1998) 63(4):241-253.
13. Dhainaut A, Tizot A, Raimbaud E, Lockhart B, Lestage P, Goldstein S: Synthesis, structure, and neuroprotective properties of novel imidazolyl nitrones. J Med Chem (2000) 43(11):2165-2175.
14. Lockhart B, Roger A, Bonhomme N, Goldstein S, Lestage P: In vivo neuroprotective effects of the novel imidazolyl nitrone free-radical scavenger (Z)-α-[(2-thiazol-2-yl)imidazole-4-yl]-N-tert-butylnitrone (S34176). Eur J Pharmacol (2005) 511(2-3):127-136.
15. Green AR, Ashwood T, Odergren T, Jackson DM: Nitrones as neuroprotective agents in cerebral ischemia with particular reference to NXY-059. Pharmacol Ther (2003) 100(3):195-214.
16. Kuroda S, Tsuchidate R, Smith ML, Maples KR, Siesjo BK: Neuroprotective effects of a novel nitrone, NXY-059, after transient focal cerebral ischemia in the rat. J Cereb Blood Flow Metab (1999) 19(7):778-787.
17. Sydserff SG, Borelli AR, Green AR, Cross AJ: Effect of NXY-059 on infarct volume after transient or permanent middle cerebral artery occlusion in the rat; studies on dose, plasma concentration and therapeutic time window. Br J Pharmacol (2002) 135(1):103-112.
18. Zhao Z, Cheng M, Maples KR, Ma JY, Buchan AM: NXY-059, a novel free radical trapping compound, reduces cortical infarction after permanent focal ischemia in the rat. Brain Res (2001) 909(1-2):46-50.
19. Marshall JW, Duffin KJ, Green AR, Ridley RM: NXY-059, a free radical-trapping agent, substantially lessens the functional disability resulting from cerebral ischemia in primate species. Stroke (2001) 32(1):190-198.
20. Marshall JW, Cummings RM, Bowes LJ, Ridley RM, Green AR: Functional and histological evidence for the protective effect of NXY-059 in a primate model of stroke when given 4 hours after occlusion. Stroke (2003) 34(9):2228-2233.
21. Lyden P, Shauib A, Ng K, Levin K, Atkinson RP, Rajput A, Wechsler L, Ashwood T, Claesson L, Odergren T, Salazar-Grueso E: Clomethiazole acute stoke study in ischemic stroke (CLASS-I): Final results. Stroke (2002) 33(1):122-128.
22. Diener HC, AlKhedr A, Busse O, Hacke W, Zingmark PH, Jonsson N, Basun H: Treatment of acute ischaemic stroke with the low-affinity, use-dependent NMDA antagonist AR-R15896AR. A safety and tolerability study. J Neurol (2002) 249(5):561-568.
23. Marshall JW, Green AR, Ridley RM: Comparison of the neuroprotective effect of clomethiazole, AR-R15896AR and NXY-059 in a primate model of stroke using histological and behavioural measures. Brain Res (2003) 972(1-2):119-126.
24. Lapchak PA, Araujo DM, Song D, Wei J, Zivin JA: Neuroprotective effects of the spin trap agent disodium-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (generic NXY-059) in a rabbit small clot embolic stroke model - combination studies with the thrombolytic tissue plasminogen activator. Stroke (2002) 33(5):1411-1415.
25. Lapchak PA, Song D, Wei J, Zivin JA: Coadministration of NXY-059 and tenecteplase six hours following embolic strokes in rabbits improved clinical rating scores. Exp Neurol (2004) 188(2):279-285.
26. Dehouck MP, Cecchelli R, Richard Green A, Renftel M, Lundquist S: In vitro blood-brain barrier permeability and cerebral endothelial cell uptake of the neuroprotective nitrone compound NXY-059 in normaxic, hypoxic and ischemic conditions. Brain Res (2002) 955 (1-2):229-235.
27. Han M, He QP, Yong G, Siesjo BK, Li PA: NXY-059, a nitrone with free radical trapping properties inhibits release of cytochrome C after cerebral ischemia. Cell Mol Biol (Noisy-le-grand) (2003) 49(8):1240-1252.
28. Edenius C, Strid S, Breitholtz-Emanuelsson A, Dalin L, Jerling M, Fransson B: NXY-059, the first nitrone being developed for stroke, is safe and well tolerated in young and elderly healthy volunteers. Cerebrovasc Dis (1999) 9:102.
29. Strid S, Borga O, Edenius C, Jostell KG, Odergren T, Weil A: Pharmacokinetics in renally impaired subjects of NXY-059, a nitrone-based, free-radical trapping agent developed for the treatment of acute stoke. Eur J Clin Pharmacol (2002) 58(6):409-415.
30. Lees KR, Sharma AK, Barer D, Ford GA, Kostulas V, Cheng Y-F, Odergren T: Tolerability and pharmacokinetics of the nitrone NXY-059 in patients with acute stroke. Stroke (2001) 32(3):675-680.
31. Lees KR, Barer D, Ford GA, Hacke W, Kostulas V, Sharma AK, Odegren T: Tolerability of NXY-059 at higher target concentrations in patients with acute stroke. Stroke (2003) 34(2):482-487.
32. Renovis Inc: Phase III trials for CEROVIVE (NXY-059) will continue as planned following interim data analysis. Press Release (2004): October 14.
33. AstraZeneca plc. First results from SAINT-1 trial show AstraZeneca's CEROVIVE (NXY-059) demonstrates a reduction in disability in patients with acute ischemia stroke. Press Release (2005):May 04.
34. Althaus JS, Fleck TJ, Becker DA, Hall ED, Vonvoigtlander PF: Azulenyl nitrones: Colorimetric detection of oxyradical end products and neuroprotection in the gerbil transient florebrain ischemia/reperfusion model. Free Radic Biol Med (1998) 24(5):738-744.
35. Klivenyi P, Matthews RT, Wermer M, Yang L, MacGarvey U, Becker DA, Natero, R, Beal MF: Azulenyl nitrone spin trap protects against MPTP neurotoxicity. Exp Neurol (1998) 152(1):163-166.
36. Becker DA, Ley JJ, Echegoyen L, Alvarado R: Stilbazulenyl nitrone (STAZN): A nitronyl-substituted hydrocarbon with the potency of classical phenolic chain-breaking antioxidants. J Am Chem Soc (2002) 124(17):4678-4684.
37. Belayev L, Becker DA, Alonso OF, Liu Y, Busto R, Ley JJ, Ginsberg MD: Stilbazulenyl nitrone, a novel azulenyl nitrone antioxidant: Improved neurological deficit and reduced contusion size after traumatic brain injury in rats. J Neurosurg (2002) 96(6):1077-1083.
38. Yang L, Calingasan NY, Chen J, Ley JJ, Becker DA, Beal MF: A novel azulenyl nitrone antioxidant protects against MPTP and 3-nitropropionic acid neurotoxicities. Exp Neurol (2005) 191(1):86-93.
39. Ginsberg MD, Becker DA, Busto R, Belayev A, Zhang Y, Khoutorova L, Ley JJ, Zhao W, Belayev L: Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia. Ann Neurol (2003) 54(3):330-342.
40. Ley JJ, Vigdorchik A, Belayev K, Zhao W, Busto R, Khoutorova L, Becker DA, Ginsberg MD: Stilbazulenyl nitrone, a second-generation azulenyl nitrone antioxidant, confers enduring neuroprotection in experimental focal cerebral ischemia in the rat: Neurobehavior, histopathology, and pharmacokinetics. J Pharmacol Exp Ther (2005) 313(3):1090-1100.