The potential of nitric oxide therapeutics in stroke

被引:39
作者
Willmot, MR [1 ]
Bath, PMW [1 ]
机构
[1] Univ Nottingham, Div Stroke Med, Nottingham NG5 1PB, England
关键词
nitric oxide; nitric oxide donors; nitric oxide synthase inhibitors; stroke; therapy;
D O I
10.1517/13543784.12.3.455
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The therapeutic modulation of the nitric oxide (NO) system has generated considerable interest as a new way for managing many disease processes. In stroke, a useful strategy is to increase NO availability and thereby exploit its beneficial antiplatelet, antiatherosclerotic, haemodynamic and neuroprotective properties. Pharmacologically, this can be achieved by providing NO substrate, using NO donors or by upregulating nitric oxide synthase. Alternatively, one can reduce NO availability by inhibiting NO synthase and thereby limiting its pro-inflammatory and neurotoxic properties. This article reviews developments in NO-related therapeutics for treatment of stroke, with a particular emphasis on compounds that are in the clinical research and development pipeline. Although the routine use of NO therapeutics for the prevention or treatment of stroke cannot currently be recommended, we are evidently at an exciting stage in their pharmacological development. Definitive randomised controlled trials in stroke patients are required as a matter of urgency.
引用
收藏
页码:455 / 470
页数:16
相关论文
共 172 条
[1]   ORAL L-ARGININE INHIBITS PLATELET-AGGREGATION BUT DOES NOT ENHANCE ENDOTHELIUM-DEPENDENT DILATION IN HEALTHY-YOUNG MEN [J].
ADAMS, MR ;
FORSYTH, CJ ;
JESSUP, W ;
ROBINSON, J ;
CELERMAJER, DS .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1995, 26 (04) :1054-1061
[2]   Recommendations for clinical trial evaluation of acute stroke therapies - Stroke Therapy Academic Industry Roundtable II (STAIR-II) [J].
Albers, GW ;
Bogousslavsky, J ;
Bozik, MA ;
Brass, LM ;
Broderick, JP ;
Fisher, M ;
Goldstein, LB ;
Salazar-Grueso, E ;
Akitsuki, S ;
Aranko, K ;
Ashwood, T ;
Atkinson, RP ;
Bell, RD ;
Brott, TG ;
Cady, WJ ;
Caplan, LR ;
Coggins, S ;
Cramer, S ;
Cyrus, P ;
Dayno, J ;
Easton, JD ;
Elliott, PJ ;
Finklestein, SP ;
Furlan, AJ ;
Gamzu, E ;
Glasky, MS ;
Gordon, K ;
Gorelick, PB ;
Greenwood, DT ;
Grotta, JC ;
Gunn, K ;
Hachinski, V ;
Hacke, W ;
Hall, ED ;
Hsu, CY ;
Humphreys, DM ;
Ishikawa, H ;
Jacobs, AJ ;
Kaste, M ;
Koroshetz, WJ ;
Krams, M ;
Lauritano, AA ;
Leclerc, J ;
Lees, KR ;
Lesko, L ;
Levine, SR ;
Levy, DE ;
Li, FH ;
Lyden, PD ;
Masayasu, H .
STROKE, 2001, 32 (07) :1598-1606
[3]   Blockade of endogenous nitric oxide production results in moderate hypertension, reducing sympathetic activity and shortening bleeding time in healthy volunteers [J].
Albert, J ;
Schedin, U ;
Lindqvist, M ;
Melcher, A ;
Hjemdahl, P ;
Frostell, C .
ACTA ANAESTHESIOLOGICA SCANDINAVICA, 1997, 41 (09) :1104-1113
[4]   Nitric oxide synthases: structure, function and inhibition [J].
Alderton, WK ;
Cooper, CE ;
Knowles, RG .
BIOCHEMICAL JOURNAL, 2001, 357 (03) :593-615
[5]   Gene transfer of endothelial nitric oxide synthase improves nitric oxide-dependent endothelial function in a hypertensive rat model [J].
Alexander, MY ;
Brosnan, MJ ;
Hamilton, CA ;
Downie, P ;
Devlin, AM ;
Dowell, F ;
Martin, W ;
Prentice, HM ;
O'Brien, T ;
Dominiczak, AF .
CARDIOVASCULAR RESEARCH, 1999, 43 (03) :798-807
[6]   Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice [J].
Amin-Hanjani, S ;
Stagliano, NE ;
Yamada, M ;
Huang, PL ;
Liao, JK ;
Moskowitz, MA .
STROKE, 2001, 32 (04) :980-985
[7]   THE EFFECT OF CHOLESTEROL-LOWERING AND ANTIOXIDANT THERAPY ON ENDOTHELIUM-DEPENDENT CORONARY VASOMOTION [J].
ANDERSON, TJ ;
MEREDITH, IT ;
YEUNG, AC ;
FREI, B ;
SELWYN, AP ;
GANZ, P .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (08) :488-493
[8]   L-NAME REDUCES INFARCT VOLUME IN A FILAMENT MODEL OF TRANSIENT MIDDLE CEREBRAL-ARTERY OCCLUSION IN THE RAT PUP [J].
ASHWAL, S ;
COLE, DJ ;
OSBORNE, S ;
OSBORNE, TN ;
PEARCE, WJ .
PEDIATRIC RESEARCH, 1995, 38 (05) :652-656
[9]  
ASHWAL S, 1993, J NEUROSURG ANESTH, V5, P241
[10]   DUAL EFFECTS OF L-NAME DURING TRANSIENT FOCAL CEREBRAL-ISCHEMIA IN SPONTANEOUSLY HYPERTENSIVE RATS [J].
ASHWAL, S ;
COLE, DJ ;
OSBORNE, TN ;
PEARCE, WJ .
AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 267 (01) :H276-H284