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Titolo:
ANXIOLYTIC ACTIVITY OF GLYCINE-B ANTAGONISTS AND PARTIAL AGONISTS - NO RELATION TO INTRINSIC ACTIVITY IN THE PATCH-CLAMP
Autore:
KARCZKUBICHA M; JESSA M; NAZAR M; PLAZNIK A; HARTMANN S; PARSONS CG; DANYSZ W;
Indirizzi:
MERZ & CO,DEPT PHARMACOL,ECKENHEIMER LANDSTR 100 D-60318 FRANKFURT GERMANY MERZ & CO,DEPT PHARMACOL D-60318 FRANKFURT GERMANY INST PSYCHIAT & NEUROL,DEPT PHARMACOL & PHYSIOL NERVOUS SYST PL-03957WARSAW POLAND MED ACAD,DEPT EXPT & CLIN PHARMACOL PL-00927 WARSAW POLAND
Titolo Testata:
Neuropharmacology
fascicolo: 10, volume: 36, anno: 1997,
pagine: 1355 - 1367
SICI:
0028-3908(1997)36:10<1355:AAOGAA>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
NMDA RECEPTOR ANTAGONISTS; ELEVATED PLUS-MAZE; DORSAL PERIAQUEDUCTAL GRAY; D-CYCLOSERINE; 1-AMINOCYCLOPROPANECARBOXYLIC ACID; SOCIAL-INTERACTION; 2 MODELS; ANTICONVULSANT ACTIVITY; GLUTAMATE RECEPTORS; SITE ANTAGONISTS;
Keywords:
VOGEL TEST; PLUS-MAZE; ANXIETY; PATCH CLAMP; NMDA RECEPTOR ANTAGONISTS; GLYCINE(B) ANTAGONISTS; GLYCINE(B) PARTIAL AGONISTS;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
66
Recensione:
Indirizzi per estratti:
Citazione:
M. Karczkubicha et al., "ANXIOLYTIC ACTIVITY OF GLYCINE-B ANTAGONISTS AND PARTIAL AGONISTS - NO RELATION TO INTRINSIC ACTIVITY IN THE PATCH-CLAMP", Neuropharmacology, 36(10), 1997, pp. 1355-1367

Abstract

On the basis of animal models, anxiety was one of the first suggestedclinical applications of partial agonists of the glycine(B) site coupled to the NMDA receptor. It is not certain, however, whether these findings can be extended to full glycine(B) antagonists and what is the relation between intrinsic activity (degree of NMDA receptor antagonism) and anxiolytic effect. In the present study several NMDA receptor antagonists, including several glycine(B) antagonists/partial agonists,were tested for anxiolytic activity in the Vogel conflict test and the elevated plus-maze. Additionally, the intrinsic activities of the glycine(B) partial agonists used [ACPC, (R,+)-HA-966 and D-cycloserine] were compared in patch-clamp experiments in cultured neurones. In the plus-maze the most striking increase in the time spent in open arms (index of anxiolytic effect) was seen after diazepam and D-cycloserine (at doses that did not change locomotion). Also reliable (dose-dependent), although weaker, anxiolytic activity was produced by the uncompetitive NMDA receptor antagonist (+)MK-801 and the competitive antagonistCGP 39551. Modest anxiolytic-like effect in the plus-maze was also observed after the glycine(B) antagonist L-701,324 and the partial agonist (+,R)-HA-966. Uncompetitive antagonists memantine and amantadine, the glycine(B) partial agonist ACPC (up to 600 mg/kg) or the full antagonists MRZ 2/570, MRZ 2/571 and MRZ 2/576 had no effect. In the Vogel conflict test neither memantine, nor any of the full glycinea antagonists tested (L-701,324 and MRZ 2/576), showed anxiolytic activity. Patch-clamp studies revealed that the intrinsic activity of (+,R)-HA-966, D-cycloserine and ACPC was 13, 57 and 92%, respectively, as compared to that of glycine itself (100%). In conclusion, for the agents tested there is no clear relation between the levels of intrinsic activity, i.e. degree of NMDA receptor inhibition, and anxiolytic activity. Moreover, L-701,324 and MRZ-type glycine(B) full antagonists do not exchibit anxiolytic activity in the elevated plus-maze and Vogel conflict test. (C) 1997 Published by Elsevier Science Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/03/20 alle ore 21:57:52