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Titolo:
DECAHYDROISOQUINOLINES - NOVEL COMPETITIVE AMPA KAINATE ANTAGONISTS WITH NEUROPROTECTIVE EFFECTS IN GLOBAL CEREBRAL-ISCHEMIA/
Autore:
ONEILL MJ; BOND A; ORNSTEIN PL; WARD MA; HICKS CA; HOO K; BLEAKMAN D; LODGE D;
Indirizzi:
ELI LILLY & CO,LILLY RES CTR LTD,ERL WOOD MANOR WINDLESHAM GU20 6PH SURREY ENGLAND LILLY CORP CTR INDIANAPOLIS IN 46285 ALLELIX BIOPHARMACEUT INC MISSISSAUGA ON L4V 1V7 CANADA
Titolo Testata:
Neuropharmacology
fascicolo: 10-11, volume: 37, anno: 1998,
pagine: 1211 - 1222
SICI:
0028-3908(1998)37:10-11<1211:D-NCAK>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMPA RECEPTOR ANTAGONISTS; D-ASPARTATE ANTAGONIST; ISCHEMIC NEURONAL INJURY; CORTICAL CELL-CULTURE; NMDA ANTAGONISTS; FOCAL ISCHEMIA; GYKI 52466; IN-VIVO; -DIHYDROXY-6-NITRO-7-SULFAMOYL-BENZO(F)QUINOXALINE NBQX; NONCOMPETITIVE ANTAGONIST;
Keywords:
AMPA ANTAGONIST; CEREBRAL ISCHEMIA; GERBIL; IGLUR5; LY293558; LY377770; NEUROPROTECTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
61
Recensione:
Indirizzi per estratti:
Citazione:
M.J. Oneill et al., "DECAHYDROISOQUINOLINES - NOVEL COMPETITIVE AMPA KAINATE ANTAGONISTS WITH NEUROPROTECTIVE EFFECTS IN GLOBAL CEREBRAL-ISCHEMIA/", Neuropharmacology, 37(10-11), 1998, pp. 1211-1222

Abstract

In the present studies, we have evaluated the activity of a series ofglutamate receptor antagonists from the decahydroisoquinoline group of compounds both in vitro and in vivo. Compound activity at lpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate receptors was assessed using ligand binding to cloned iGluR2 and iGluR5 receptors and on responses evoked by AMPA and N-methyl-D-aspartate (NMDA)in the cortical wedge preparation. In vivo, compounds were examined for antagonist activity electrophysiologically in the rat spinal cord preparation and in the gerbil model of global cerebral ischaemia. Compounds tested were LY293558, which has been shown to protect in models of focal cerebral ischaemia, LY202157 (an NMDA antagonist), LY246492 (an NMDA and AMPA receptor antagonist), LY302679, LY292025, LY307190, LY280263, LY289178, LY289525, LY294486 (AMPA/kainate antagonists) and LY382884 (an iGluR5 selective antagonist). Results obtained support a role for AMPA receptors in cerebral ischemia. LY377770 (a mixed AMPA/iGluR5 antagonist and active isomer of LY294486) demonstrated good neuroprotection with a 2-h time window and may therefore be useful in the treatment of ischaemic conditions. (C) 1998 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 09:32:58