Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
ACTIVITY OF 2,3-BENZODIAZEPINES AT NATIVE RAT AND RECOMBINANT HUMAN GLUTAMATE RECEPTORS IN-VITRO - STEREOSPECIFICITY AND SELECTIVITY PROFILES
Autore:
BLEAKMAN D; BALLYK BA; SCHOEPP DD; PALMER AJ; BATH CP; SHARPE EF; WOOLLEY ML; BUFTON HR; KAMBOJ RK; TARNAWA I; LODGE D;
Indirizzi:
ELI LILLY & CO,LILLY RES CTR LTD,ERL WOOD MANOR,SUNNINGHILL RD WINDLESHAM GU20 6PH SURREY ENGLAND ALLELIX BIOPHARMACEUT INC MISSISSAUGA ON L4V 1V7 CANADA ELI LILLY & CO,LILLY RES LABS INDIANAPOLIS IN 46285 UNIV BRISTOL,DEPT PHARMACOL BRISTOL BS8 1TD AVON ENGLAND INST DRUG RES H-1325 BUDAPEST HUNGARY
Titolo Testata:
Neuropharmacology
fascicolo: 12, volume: 35, anno: 1996,
pagine: 1689 - 1702
SICI:
0028-3908(1996)35:12<1689:AO2ANR>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHARMACOLOGICAL CHARACTERIZATION; HIPPOCAMPAL-NEURONS; KAINATE RECEPTORS; AMPA; CYCLOTHIAZIDE; ANTAGONISM; DESENSITIZATION; EXPRESSION; GYKI-52466; MODULATION;
Keywords:
GYKI52466; GYKI53655; GYKI53405; LY300168; LY293606; PURKINJE NEURONS; GLUR1; GLUR4; GLUR5; GLUR6; GLUR6+KA2; DORSAL ROOT GANGLION; CORTICAL WEDGE; NMDA; SPINAL CORD;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
38
Recensione:
Indirizzi per estratti:
Citazione:
D. Bleakman et al., "ACTIVITY OF 2,3-BENZODIAZEPINES AT NATIVE RAT AND RECOMBINANT HUMAN GLUTAMATE RECEPTORS IN-VITRO - STEREOSPECIFICITY AND SELECTIVITY PROFILES", Neuropharmacology, 35(12), 1996, pp. 1689-1702

Abstract

The activity and selectivity of the glutamate receptor antagonists belonging to the 2,3-benzodiazepine class of compounds have been examined at recombinant human non-NMDA glutamate receptors expressed in HEK293 cells and on native rat NMDA and non-NMDA receptors in vitro. The racemic 2,3-benzodiazepines GYKI52466, LY293606 (GYKI53405) and LY300168(GYKI53655) inhibited AMPA (10 mu M)-mediated responses in recombinant human GluR1 receptors expressed in HEK293 cells with approximate IC50 values of 18 mu M, 24 mu M and 6 mu M, respectively and AMPA (10 mu M) responses in recombinant human GluR4 expressing HEK293 cells with approximate IC50 values of 22 mu M, 28 mu M and 5 mu M, respectively. GYKI 52466, LY293606 and LY300168 were non-competitive antagonists of AMPA receptor-mediated responses in acutely isolated rat cerebellar Purkinje neurons with approximate IC50 values of 10 mu M, 8 mu M and 1.5 mu M, respectively. The activity of racemic compounds LY293606 and LY300168 was established to reside in the (-) isomer of each compound. Ata concentration of 100 mu M, GYKI52466, LY293606 and LY300168 produced <30% inhibition of kainate-activated currents evoked in HEK293 cellsexpressing either human homomeric GluR5 or GluR6 receptors or heteromeric GluR6+KA2 kainate receptors. The activity of the 2,3-benzodiazepines at 100 mu M was weak at kainate receptors, but was stereoselective. Similar levels of inhibition were observed for kainate-induced currents in dorsal root ganglion neurons. Intact tissue preparations were also used to examine the stereoselective actions of the 2,3-benzodiazepines. In the cortical wedge preparation, the active isomer of LY300168, LY303070, produced a non-competitive antagonism of AMPA-evoked depolarizations with smaller changes in depolarizations induced by kainate and no effect on NMDA-dependent depolarizations. LY303070 was also effective in preventing 30 mu M AMPA-induced depolarizations in isolated spinal cord dorsal roots with an approximate IC50 value of 1 mu M. Synaptic transmission in the hemisected spinal cord preparation was stereoselectively antagonized by the active isomers of LY300168 and LY293606. In summary, these results indicate that 2,3-benzodiazepines are potent, selective and stereospecific antagonists of the AMPA subtype of the non-NMDA glutamate receptor. (C) 1997 Elsevier Science Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 01:41:04