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Titolo:
THE ATYPICAL NEUROLEPTIC PROFILE OF THE GLYCINE N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST, L-701,324, IN RODENTS/
Autore:
BRISTOW LJ; FLATMAN KL; HUTSON PH; KULAGOWSKI JJ; LEESON PD; YOUNG L; TRICKLEBANK MD;
Indirizzi:
MERCK SHARP & DOHME LTD,RES LABS,NEUROSCI RES CTR,TERLINGS PK,EASTWICK RD HARLOW CM20 2QR ESSEX ENGLAND
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 2, volume: 277, anno: 1996,
pagine: 578 - 585
SICI:
0022-3565(1996)277:2<578:TANPOT>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
MESOLIMBIC DOPAMINE SYSTEM; INDUCED LOCOMOTOR-ACTIVITY; RAT NUCLEUS ACCUMBENS; NMDA RECEPTORS; ANTIPSYCHOTIC-DRUGS; PHENCYCLIDINE PCP; ACOUSTIC STARTLE; CORPUS STRIATUM; BINDING-SITES; AMINO-ACIDS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
66
Recensione:
Indirizzi per estratti:
Citazione:
L.J. Bristow et al., "THE ATYPICAL NEUROLEPTIC PROFILE OF THE GLYCINE N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST, L-701,324, IN RODENTS/", The Journal of pharmacology and experimental therapeutics, 277(2), 1996, pp. 578-585

Abstract

The present study has examined the glycine/N-methyl-D-aspartate antagonist, L-701,324 loro-4-hydroxy-3-(3-phenoxy)-phenyl-2(H)quinolone] inrodent behavioral tests commonly used to predict antipsychotic potential and side effect liability in humans. Pretreatment with L-701,324 dose-dependently antagonized amphetamine-induced hyperactivity in the mouse (ED(50) = 1.12 +/- 0.45 mg/kg p.o.), an effect which was similar to that of the classical neuroleptic, haloperidol, and the atypical neuroleptic, clozapine. In addition, p.o. administration of L-701,324 (2.5 or 5 mg/kg) attenuated the hyperactivity response induced by amphetamine infusion into the rat nucleus accumbens. In contrast to haloperidol, however, stereotyped sniffing and licking/biting, induced by either the systemic administration of apomorphine or infusion of amphetamine into the striatum, was not altered in rats pretreated with L-701,324 (30 or 100 mg/kg p.o.). Furthermore, L-701,324 failed to impair spontaneous locomotor activity or induce catalepsy in the mouse at doses greater than or equal to 100 mg/kg. Although a significant reduction inspontaneous activity was observed in rats pretreated with L-701,324, the minimum effective dose (10 mg/kg p.o.) was 2-fold greater than that which abolished amphetamine-induced hyperactivity in this species. Thus, L-701,324 selectively blocks behaviors associated with the activation of the mesolimbic dopamine system suggesting that glycine/N-methyl-D-aspartate receptor antagonists may offer a novel approach to the treatment of schizophrenia in humans.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 07:53:39