Neuroprotective effects of a systemically active Group II metabotropic glutamate receptor agonist LY354740 in a gerbil model of global ischaemia

被引:72
作者
Bond, A
O'Neill, MJ
Hicks, CA
Monn, JA
Lodge, D
机构
[1] Eli Lilly & Co, Lilly Res Ctr, Windlesham GU20 6PH, Surrey, England
[2] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA
关键词
global ischaemia; metabotropic glutamate receptor; neuroprotection;
D O I
10.1097/00001756-199804200-00042
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
THE neuroprotective effects of a novel Group II metabotropic glutamate receptor (mGluR) agonist, LY354740, have been evaluated in a gerbil model of global ischaemia. When administered at 50 mg/kg, i.p., 30 min and 6 h after a 3 min period of bilateral carotid artery occlusion (BCAO), the compound reduced the damage to CA1 hippocampal neurones to a significant level. However, when the ischaemic insult was made more severe, by increasing the period of occlusion to 4 and 5 min, the neuroprotective effects of LY354740 were reduced. From these findings, it would appear that Group II mGluRs may play a role in ischaemic damage in the gerbil hippocampus and that agonists at these receptors are potential neuroprotective agents. (C) 1998 Rapid Science Ltd.
引用
收藏
页码:1191 / 1193
页数:3
相关论文
共 23 条
[1]   In vivo inhibition of veratridine-evoked release of striatal excitatory amino acids by the group II metabotropic glutamate receptor agonist LY354740 in rats [J].
Battaglia, G ;
Monn, JA ;
Schoepp, DD .
NEUROSCIENCE LETTERS, 1997, 229 (03) :161-164
[2]  
BLEAKMAN D, 1992, MOL PHARMACOL, V42, P192
[3]   THE N-METHYL-D-ASPARTATE ANTAGONISTS CGS-19755 AND CPP REDUCE ISCHEMIC BRAIN-DAMAGE IN GERBILS [J].
BOAST, CA ;
GERHARDT, SC ;
PASTOR, G ;
LEHMANN, J ;
ETIENNE, PE ;
LIEBMAN, JM .
BRAIN RESEARCH, 1988, 442 (02) :345-348
[4]   PHARMACOLOGY OF METABOTROPIC GLUTAMATE RECEPTOR-MEDIATED ENHANCEMENT OF RESPONSES TO EXCITATORY AND INHIBITORY AMINO-ACIDS ON RAT SPINAL NEURONS IN-VIVO [J].
BOND, A ;
LODGE, D .
NEUROPHARMACOLOGY, 1995, 34 (08) :1015-1023
[5]   A novel orally active group 2 metabotropic glutamate receptor agonist: LY354740 [J].
Bond, A ;
Monn, JA ;
Lodge, D .
NEUROREPORT, 1997, 8 (06) :1463-1466
[6]  
BRIERLEY TB, 1976, GREENFIELDS NEUROPAT, P41
[7]   Activation of group III metabotropic glutamate receptors is neuroprotective in cortical cultures [J].
Bruno, V ;
Copani, A ;
Bonanno, L ;
Knoepfel, T ;
Kuhn, R ;
Roberts, PJ ;
Nicoletti, F .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1996, 310 (01) :61-66
[8]  
Bruno V, 1997, J NEUROSCI, V17, P1891
[9]   ACTIVATION OF METABOTROPIC RECEPTORS HAS A NEUROPROTECTIVE EFFECT IN A RODENT MODEL OF FOCAL ISCHEMIA [J].
CHIAMULERA, C ;
ALBERTINI, P ;
VALERIO, E ;
REGGIANI, A .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1992, 216 (02) :335-336
[10]  
GILL R, 1987, J NEUROSCI, V7, P3343