scholarly journals NXY-059, a Free Radical–Trapping Agent, Substantially Lessens the Functional Disability Resulting From Cerebral Ischemia in a Primate Species

Stroke ◽  
2001 ◽  
Vol 32 (1) ◽  
pp. 190-198 ◽  
Author(s):  
Jonathan W. B. Marshall ◽  
Katharine J. Duffin ◽  
A. Richard Green ◽  
Rosalind M. Ridley
Keyword(s):  
Free Radical ◽  
Cerebral Ischemia ◽  
Functional Disability ◽  
Primate Species ◽  
Radical Trapping ◽  
Trapping Agent

scholarly journals NXY-059, the free radical trapping nitrone-based agent, reduces hemiparesis and reduces grey and white matter damage after focal cerebral ischemia in monkeys

Stroke ◽  
2001 ◽  
Vol 32 (suppl_1) ◽  
pp. 327-327
Author(s):  
J Wb Marshall ◽  
K J Duffin ◽  
A R Green ◽  
R M Ridley
Keyword(s):  
Free Radical ◽  
White Matter ◽  
Acute Stroke ◽  
Functional Disability ◽  
Focal Cerebral Ischemia ◽  
Spatial Neglect ◽  
Histopathological Analysis ◽  
White Matter Damage ◽  
Radical Trapping ◽  
Published Evidence

60 There is little published evidence for protection of white matter with neuroprotective drugs in animal models of stroke, yet white matter protection may be important in achieving clinical efficacy. We have examined the effects of NXY-059, a nitrone-based free radical trapping agent, on long-term functional disability in a primate model of stroke. We also examined histopathological effects, including analyses of grey and white matter damage. Five minutes after unilateral permanent middle cerebral artery occlusion, marmosets received a 1 ml i.v. infusion of saline (n=5) or NXY-059 (28 mg/kg) (n=6) and osmotic minipumps (model 2001D) were implanted s.c. to provide continuous drug or saline infusion for 48 h. Drug-filled pumps released NXY-059 at a rate of approximately 16 mg/kg/h. The plasma unbound drug concentration at 24 h was 76.3 ± 5.7 μM, a level well tolerated in acute stroke patients. The monkeys had been trained and tested on a variety of behavioral tasks before surgery. NXY-059-treated monkeys were significantly better at reaching with their contralesional arm than were saline-treated monkeys when re-tested 3 (p<0.01) and 10 weeks (p<0.01) after surgery. NXY-059-treatment also significantly reduced spatial neglect measured 3 weeks after surgery (p<0.01) compared with the saline group. After behavioral testing was complete, histopathological analysis showed NXY-059-treated monkeys had significantly smaller infarcts than saline-treated monkeys (F (1, 10)=5.21, p<0.05). NXY-059 reduced overall infarct size by 51%, damage to the cortex was reduced by 54%, white matter by 52%, caudate by 49%, and putamen by 33% compared with saline-treated monkeys. In conclusion, NXY-059 substantially lessened the functional disability in these monkeys. This drug protects not only cortical tissue, but also white matter and subcortical structures against ischemic damage. Together these findings bode well for advancing this drug to further clinical trials for its use in acute stroke.

scholarly journals New Method in Free Radical Chemistry Using 2,4-Diphenyl-4-methyl-1-pentene as Radical Trapping Agent

1997 ◽  
Vol 29 (4) ◽  
pp. 366-369 ◽  
Author(s):  
Yasumasa Watanabe ◽  
Hideyo Ishigaki ◽  
Hiroshi Okada ◽  
Shuji Suyama
Keyword(s):  
Free Radical ◽  
New Method ◽  
Radical Chemistry ◽  
Radical Trapping ◽  
Free Radical Chemistry ◽  
Trapping Agent

Pharmacokinetics of NXY-059, a nitrone-based free radical trapping agent, in healthy young and elderly subjects

2002 ◽  
Vol 11 (1) ◽  
pp. 34-42 ◽  
Author(s):  
Charlotte Edenius ◽  
Stig Strid ◽  
Olof Borgå ◽  
Anna Breitholtz-Emanuelsson ◽  
Kerstin Lanbeck Vallén ◽  
...  
Keyword(s):  
Free Radical ◽  
Elderly Subjects ◽  
Radical Trapping ◽  
Young And Elderly Subjects ◽  
Trapping Agent

Efficacy of disodium 4-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059), a free radical trapping agent, in a rat model of hemorrhagic stroke

2001 ◽  
Vol 40 (3) ◽  
pp. 433-439 ◽  
Author(s):  
James Peeling ◽  
Marc R Del Bigio ◽  
Dale Corbett ◽  
A.Richard Green ◽  
David M Jackson
Keyword(s):  
Free Radical ◽  
Rat Model ◽  
Hemorrhagic Stroke ◽  
Radical Trapping ◽  
Trapping Agent ◽  
Methyl Benzene

Synthesis of the radical scavenger 1,1,3,3-Tetramethylisoindolin-2-yloxyl

1983 ◽  
Vol 36 (2) ◽  
pp. 397 ◽  
Author(s):  
PG Griffiths ◽  
G Moad ◽  
E Rizzardo
Keyword(s):  
Free Radical ◽  
Small Proportion ◽  
Radical Scavenger ◽  
Grignard Reaction ◽  
Radical Trapping ◽  
Methylmagnesium Iodide ◽  
Trapping Agent

A versatile free-radical trapping agent, 1,1,3,3-tetramethylisoindolin-2-yloxyl, has been prepared from N-benzylphthalimide by reaction with 'methylmagnesium iodide' in refluxing toluene followed by hydrogenolysis and oxidation. The Grignard reaction gives 2-benzyl-1,1,3,3-tetramethylisoindoline along with a small proportion of an unexpected by-product, 2-benzyl-1-ethyl-1,3,3-trimethyliso-indoline.

Pharmacokinetics in renally impaired subjects of NXY-059, a nitrone-based, free-radical trapping agent developed for the treatment of acute stroke

2002 ◽  
Vol 58 (6) ◽  
pp. 409-415 ◽  
Author(s):  
Stig Strid ◽  
Olof Borgå ◽  
Charlotte Edenius ◽  
Karl-Gustav Jostell ◽  
Tomas Odergren ◽  
...  
Keyword(s):  
Free Radical ◽  
Acute Stroke ◽  
Radical Trapping ◽  
Trapping Agent

NXY-059, a novel free radical trapping compound, reduces cortical infarction after permanent focal cerebral ischemia in the rat

2001 ◽  
Vol 909 (1-2) ◽  
pp. 46-50 ◽  
Author(s):  
Zonghang Zhao ◽  
Mingshan Cheng ◽  
Kirk R. Maples ◽  
Jing Ying Ma ◽  
Alastair M. Buchan
Keyword(s):  
Free Radical ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Cortical Infarction ◽  
Radical Trapping
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