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Titolo:
S33084, a novel, potent, selective, and competitive antagonist at dopamineD-3-receptors: I. Receptorial, electrophysiological and neurochemical profile compared with GR218,231 and L741,626
Autore:
Millan, MJ; Gobert, A; Newman-Tancredi, A; Lejeune, F; Cussac, D; Rivet, JM; Audinot, V; Dubuffet, T; Lavielle, G;
Indirizzi:
Ctr Rech Croissy, Inst Rech Servier, Dept Psychopharmacol, F-78290 CroissySur Seine, France Ctr Rech Croissy Croissy Sur Seine France F-78290 oissySur Seine, France Ctr Rech Croissy, Inst Rech Servier, Dept Chem, F-78290 Croissy Sur Seine,France Ctr Rech Croissy Croissy Sur Seine France F-78290 oissy Sur Seine,France
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 3, volume: 293, anno: 2000,
pagine: 1048 - 1062
SICI:
0022-3565(200006)293:3<1048:SANPSA>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
HAMSTER OVARY CELLS; D-3 RECEPTOR; DEFICIENT MICE; HIGH-AFFINITY; AUTORECEPTOR FUNCTION; ANTIPSYCHOTIC AGENTS; INVERSE AGONISTS; FRONTAL-CORTEX; RAT-BRAIN; RELEASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Millan, MJ Ctr Rech Croissy, Inst Rech Servier, Dept Psychopharmacol, 125 Chemin de Ronde, F-78290 Croissy Sur Seine, France Ctr Rech Croissy 125 Chemin de Ronde Croissy Sur Seine France F-78290
Citazione:
M.J. Millan et al., "S33084, a novel, potent, selective, and competitive antagonist at dopamineD-3-receptors: I. Receptorial, electrophysiological and neurochemical profile compared with GR218,231 and L741,626", J PHARM EXP, 293(3), 2000, pp. 1048-1062

Abstract

The benzopyranopyrrole S33084 displayed pronounced affinity (pK(i) = 9.6) for cloned human hD(3)-receptors, and >100-fold lower affinity for hD(2) and all other receptors (>30) examined. S33084 concentration dependently, potently, and competitively (pA(2)= 9.7) antagonized dopamine (DA)-induced [S-35]guanosine-5'- O-(3-thio)triphosphate (GTP gamma S) binding at hD(3)-receptors. It also concentration dependently abolished stimulation by DA of hD(3)-receptor-coupled mitogen-activated protein kinase. Administered alone, S33084 did not modify dialysate levels of DA in the frontal cortex, nucleus accumbens, or striatum of freely moving rats, nor the firing rate of ventrotegmental dopaminergic cell bodies. Furthermore, it had minimal effect on DA turn-over in mesocortical, mesolimbic, and nigrostriatal projection regions. However, S33084 dose dependently blocked the suppressive influence of the preferential D-3-agonist PD128,907 on frontocortical release of DA. Furthermore, it likewise antagonized the inhibitory influence of PD128,907 on the electrical activity of ventrotegmental dopaminergic neurons. Although less potent than S33084, GR218,231 likewise behaved as a selective hD(3)- versus hD(2)-receptor antagonist and its neurochemical and electrophysiological profiles were similar. In contrast, L741,626 was a preferential antagonist at hD(2) versus hD(3) sites. in vivo, on administration alone, L741,626 increased frontocortical, mesolimbic, and (more potently) striatal DA release, enhanced the firing rate of dopaminergic perikarya, and accelerated cerebral DA synthesis. It also blocked the actions of PD128,907. In conclusion,S33084 is a novel, potent, selective, and competitive antagonist at hD(3)-receptors. Although GR218,231 behaves similarly, L741,626 is a preferentialD-2-receptor antagonist. DA D-2- but not D-3-(auto) receptors tonically inhibit ascending dopaminergic pathways, although the latter may contribute to phasic suppression of DA release in frontal cortex.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 14:40:02