THE NMDA RECEPTOR ANTAGONIST ELIPRODIL (SL-82.0715) BLOCKS VOLTAGE-OPERATED CA2+ CHANNELS IN RAT CULTURED CORTICAL-NEURONS

被引：36

作者：

BITON, B ^{[1
]}

GRANGER, P ^{[1
]}

CARREAU, A ^{[1
]}

DEPOORTERE, H ^{[1
]}

SCATTON, B ^{[1
]}

AVENET, P ^{[1
]}

机构：

[1] SYNTHELABO RECH,DEPT PRECLIN RES,F-92220 BAGNEUX,FRANCE

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1994年 / 257卷 / 03期

关键词：

NMDA RECEPTOR; CA2+ CHANNEL; VOLTAGE-CLAMP; WHOLE-CELL; CORTICAL NEURON; CULTURED; ELIPRODIL;

D O I：

10.1016/0014-2999(94)90142-2

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The effect of the non-competitive NMDA receptor antagonist eliprodil on NMDA receptor- and voltage-operated Ca2+ currents was investigated in rat cultured cortical neurons by using the whole-cell patch clamp technique. With neurons voltage-clamped at -40 mV, eliprodil reduced in a concentration-dependent manner the inward current induced by N-methyl-D-aspartate (NMDA) (10 mu M) in the presence of D-serine with an IC50 of 0.67 mu M (I-max = 83%). Eliprodil also blocked the total inward Ba2+ current carried in part by L- and N-type Ca2+ channels with an IC50 of 1.48 mu M (I-max = 87%). These results suggest that the neuroprotective properties of eliprodil could be due to its combined ability to antagonize the NMDA receptor- and voltage-operated Ca2+ channels.

引用

页码：297 / 301

页数：5

共 13 条

[1]

CARTER C, 1991, EXCITATORY AMINO ACI, P130

[2] CALCIUM-MEDIATED NEUROTOXICITY - RELATIONSHIP TO SPECIFIC CHANNEL TYPES AND ROLE IN ISCHEMIC DAMAGE [J].

CHOI, DW .

TRENDS IN NEUROSCIENCES, 1988, 11 (10) :465-469

[3]

LEGENDRE P, 1991, MOL PHARMACOL, V40, P289

[4] DEXTROMETHORPHAN BLOCKS N-METHYL-D-ASPARTATE-INDUCED CURRENTS AND VOLTAGE-OPERATED INWARD CURRENTS IN CULTURED CORTICAL-NEURONS [J].

NETZER, R ;

PFLIMLIN, P ;

TRUBE, G .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1993, 238 (2-3) :209-216

[5] N-METHYL-D-ASPARTATE RECEPTOR ANTAGONISTS - A NOVEL THERAPEUTIC PERSPECTIVE FOR THE TREATMENT OF ISCHEMIC BRAIN INJURY [J].

SCATTON, B ;

CARTER, C ;

BENAVIDES, J ;

GIROUX, C .

CEREBROVASCULAR DISEASES, 1991, 1 (03) :121-135

[6] POLYAMINES ALLOSTERICALLY MODULATE [H-3] NITRENDIPINE BINDING TO THE VOLTAGE-SENSITIVE CALCIUM-CHANNEL IN RAT-BRAIN [J].

SCHOEMAKER, H .

EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 1992, 225 (02) :167-169

[7] INTERACTIONS OF POLYAMINES WITH NEURONAL ION CHANNELS [J].

SCOTT, RH ;

SUTTON, KG ;

DOLPHIN, AC .

TRENDS IN NEUROSCIENCES, 1993, 16 (04) :153-160

[8] PATHOPHYSIOLOGY AND TREATMENT OF FOCAL CEREBRAL-ISCHEMIA .2. MECHANISMS OF DAMAGE AND TREATMENT [J].

SIESJO, BK .

JOURNAL OF NEUROSURGERY, 1992, 77 (03) :337-354

[9] PREVENTION BY ELIPRODIL (SL-82.0715) OF TRAUMATIC BRAIN-DAMAGE IN THE RAT - EXISTENCE OF A LARGE (18-H) THERAPEUTIC WINDOW [J].

TOULMOND, S ;

SERRANO, A ;

BENAVIDES, J ;

SCATTON, B .

BRAIN RESEARCH, 1993, 620 (01) :32-41

[10] ANTAGONISM BY NG-NITRO-L-ARGININE OF L-GLUTAMATE-INDUCED NEUROTOXICITY IN CULTURED NEONATAL RAT CORTICAL-NEURONS - PROLONGED APPLICATION ENHANCES NEUROPROTECTIVE EFFICACY [J].

VIGE, X ;

CARREAU, A ;

SCATTON, B ;

NOWICKI, JP .

NEUROSCIENCE, 1993, 55 (04) :893-901

← 1 2 →