SP-8203 shows neuroprotective effects and improves cognitive impairment in ischemic brain injury through NMDA receptor

被引：19

作者：

Noh, Su-Jin ^{[1
,2
]}

Lee, Jong Min ^{[3
]}

Lee, Ki Sung ^{[3
]}

Hong, Hyun Su ^{[3
]}

Lee, Chul Kyu ^{[3
]}

Cho, Il Hwan ^{[3
]}

Kim, Hye-Sun ^{[1
,2
]}

Suh, Yoo-Hun ^{[1
,2
]}

机构：

[1] Seoul Natl Univ, Coll Med, Dept Pharmacol, Natl Creat Res Initiat Ctr Alzheimers Dementia, Seoul, South Korea

[2] Seoul Natl Univ, Neurosci Res Inst, MRC, Seoul, South Korea

[3] Shinpoong Pharmaceut Co Ltd, Cent Res Inst, Ansan, Kyunggi Do, South Korea

来源：

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR | 2011年 / 100卷 / 01期

关键词：

Cerebral ischemia; Earth worms; Excitotoxicity; Memory; Neuronal death; NMDA; D-ASPARTATE RECEPTORS; MIDDLE CEREBRAL-ARTERY; GLUTAMATE NEUROTOXICITY; SPATIAL MEMORY; RAT MODEL; SPERMINE; DAMAGE; FEAR; ANTAGONISTS; POLYAMINES;

D O I：

10.1016/j.pbb.2011.07.018

中图分类号：

B84 [心理学]; C [社会科学总论]; Q98 [人类学];

学科分类号：

03 ; 0303 ; 030303 ; 04 ; 0402 ;

摘要：

The extracts of earth worms, Eisenia andrei, have been used as a therapeutic agent for stroke in the traditional medicine. It is also reported that the protease fraction separated from the extracts has strong anti-thrombotic activity. Besides anti-thrombotic actions, we found that SP-8203, N-[3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl]-N-{4-[3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylamino]butyl}acetamide, derived from the extracts of earth worms blocked N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity in a competitive manner. The neuroprotective effects of SP-8203 were attributable to prevention of Ca2+ influx through NMDA receptors. The systemic administration of SP-8203 markedly reduced neuronal death following middle cerebral artery occlusion in rats. SP-8203 significantly improved spatial learning and memory in the water maze test. These results provided strong pharmacological basis for its potential therapeutic roles in cerebral ischemia. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：73 / 80

页数：8

共 41 条

[1] NMDA receptor blockade and hippocampal neuronal loss impair fear conditioning and position habit reversal in C57Bl/6 mice [J].

Bardgett, ME ;

Boeckman, R ;

Krochmal, D ;

Fernando, H ;

Ahrens, R ;

Csernansky, JG .

BRAIN RESEARCH BULLETIN, 2003, 60 (1-2) :131-142

[2] COMPETITIVE AND NONCOMPETITIVE NMDA RECEPTOR ANTAGONISTS IN SPATIAL-LEARNING TASKS [J].

BISCHOFF, C ;

TIEDTKE, PI .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1992, 213 (02) :269-273

[3] CHARACTERIZATION OF SPECIFIC, HIGH-AFFINITY BINDING-SITES FOR GLUTAMIC-LABELED ACID IN RAT-BRAIN MEMBRANES [J].

BIZIERE, K ;

THOMPSON, H ;

COYLE, JT .

BRAIN RESEARCH, 1980, 183 (02) :421-433

[4] Ligands for glutamate receptors:: Design and therapeutic prospects [J].

Bräuner-Osborne, H ;

Egebjerg, J ;

Nielsen, EO ;

Madsen, U ;

Krogsgaard-Larsen, P .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (14) :2609-2645

[5] Systemic administration of polyaminergic agents modulate fear conditioning in rats [J].

Camera, Keli ;

Mello, Carlos Fernando ;

Chiapinotto Ceretta, Ana Paula ;

Rubin, Maribel Antonello .

PSYCHOPHARMACOLOGY, 2007, 192 (04) :457-464

[6] GLUTAMATE NEUROTOXICITY AND DISEASES OF THE NERVOUS-SYSTEM [J].

CHOI, DW .

NEURON, 1988, 1 (08) :623-634

[7]

CHOI DW, 1987, J NEUROSCI, V7, P357

[8] Neuroprotective effects of spermine following hypoxia-ischemia-induced brain damage: A mechanistic study [J].

Clarkson, AN ;

Liu, HZ ;

Pearson, L ;

Kapoor, M ;

Harrison, JC ;

Sammut, IA ;

Jackson, DM ;

Appleton, I .

FASEB JOURNAL, 2004, 18 (07) :1114-+

[9] MEMORIES OF NMDA RECEPTORS AND LTP [J].

COLLINGRIDGE, GL ;

BLISS, TVP .

TRENDS IN NEUROSCIENCES, 1995, 18 (02) :54-56

[10] Brain lesions and delayed water maze learning deficits after intracerebroventricular spermine [J].

Conway, EL .

BRAIN RESEARCH, 1998, 800 (01) :10-20

← 1 2 3 4 5 →