The importance of voltage-dependent sodium channels in cerebral ischaemia

被引:29
作者
Carter, AJ [1 ]
机构
[1] Boehringer Ingelheim KG, Dept Cent Nervous Syst Res, D-55216 Ingelheim, Germany
关键词
neuroprotection; reperfusion; Na+ channels; NMDA receptors; ischaemia; thromboembolic stroke;
D O I
10.1007/BF01345257
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Strategies for the treatment of thromboembolic stroke are based on restoring the blood flow as soon as possible and protecting the neurons from the deleterious consequences of cerebral ischaemia. Interest has focused on blockers of voltage-dependent Na+ channels as potential neuroprotective agents because they prevent neuronal death in various experimental models of cerebral ischaemia and act cytoprotectively in models of white matter damage. Although several Na+ blockers are currentry being tested in various phases of clinical development, most of these agents are relatively weak and unspecific. I therefore consider it worthwhile to search for molecules which specifically block voltage-dependent Na+ channels for the treatment of cerebral ischaemia.
引用
收藏
页码:159 / 169
页数:11
相关论文
共 89 条
[1]   SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF THE N-METHYL-D-ASPARTATE ANTAGONIST DEXTRORPHAN IN PATIENTS WITH ACUTE STROKE [J].
ALBERS, GW ;
ATKINSON, RP ;
KELLEY, RE ;
ROSENBAUM, DM .
STROKE, 1995, 26 (02) :254-258
[2]   REDUCTION BY LIFARIZINE OF THE NEURONAL DAMAGE-INDUCED BY CEREBRAL-ISCHEMIA IN RODENTS [J].
ALPS, BJ ;
CALDER, C ;
WILSON, AD ;
MCBEAN, DE ;
ARMSTRONG, JM .
BRITISH JOURNAL OF PHARMACOLOGY, 1995, 115 (08) :1439-1446
[3]   THE DISSOCIATIVE ANESTHETICS, KETAMINE AND PHENCYCLIDINE, SELECTIVELY REDUCE EXCITATION OF CENTRAL MAMMALIAN NEURONS BY N-METHYL-ASPARTATE [J].
ANIS, NA ;
BERRY, SC ;
BURTON, NR ;
LODGE, D .
BRITISH JOURNAL OF PHARMACOLOGY, 1983, 79 (02) :565-575
[4]  
[Anonymous], DRUG NEWS PERSPECT
[5]   Combined neuroprotection and reperfusion therapy for stroke - Effect of lubeluzole and diaspirin cross-linked hemoglobin in experimental focal ischemia [J].
Aronowski, J ;
Strong, R ;
Grotta, JC .
STROKE, 1996, 27 (09) :1571-1576
[6]   GRADED BIOASSAY FOR DEMONSTRATION OF BRAIN RESCUE FROM EXPERIMENTAL ACUTE-ISCHEMIA IN RATS [J].
ARONOWSKI, J ;
OSTROW, P ;
SAMWAYS, E ;
STRONG, R ;
ZIVIN, JA ;
GROTTA, JC .
STROKE, 1994, 25 (11) :2235-2240
[7]   NONVESICULAR RELEASE OF NEUROTRANSMITTER [J].
ATTWELL, D ;
BARBOUR, B ;
SZATKOWSKI, M .
NEURON, 1993, 11 (03) :401-407
[8]   CLINICAL EXAMINATION IN DIAGNOSIS AND SUBCLASSIFICATION OF STROKE [J].
BAMFORD, J .
LANCET, 1992, 339 (8790) :400-402
[9]  
Barinaga M, 1996, SCIENCE, V272, P664
[10]   ELEVATION OF THE EXTRACELLULAR CONCENTRATIONS OF GLUTAMATE AND ASPARTATE IN RAT HIPPOCAMPUS DURING TRANSIENT CEREBRAL-ISCHEMIA MONITORED BY INTRACEREBRAL MICRODIALYSIS [J].
BENVENISTE, H ;
DREJER, J ;
SCHOUSBOE, A ;
DIEMER, NH .
JOURNAL OF NEUROCHEMISTRY, 1984, 43 (05) :1369-1374