Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Effects of recent and reference antipsychotic agents at human dopamine D-2and D-3 receptor signaling in Chinese hamster ovary cells
Autore:
Vanhauwe, JFM; Ercken, M; van de Wiel, D; Jurzak, M; Leysen, JE;
Indirizzi:
Janssen Pharmaceut Ext 2619, B-2340 Beerse, Belgium Janssen Pharmaceut Ext2619 Beerse Belgium B-2340 B-2340 Beerse, Belgium
Titolo Testata:
PSYCHOPHARMACOLOGY
fascicolo: 4, volume: 150, anno: 2000,
pagine: 383 - 390
Fonte:
ISI
Lingua:
ENG
Soggetto:
IN-VITRO; BINDING; DRUGS; RISPERIDONE; EXPRESSION; ACTIVATION; AGONIST; LINES; VIVO;
Keywords:
sdopamine receptor; [S-35]-GTP gamma S binding; cAMP assay; haloperidol; risperidone; pipamperone; zotepine; olanzapine; sertindole; clozapine; quetiapine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Leysen, JE Janssen Pharmaceut Ext 2619, Turnhoutseweg 30, B-2340 Beerse, Belgium Janssen Pharmaceut Ext 2619 Turnhoutseweg 30 Beerse Belgium B-2340
Citazione:
J.F.M. Vanhauwe et al., "Effects of recent and reference antipsychotic agents at human dopamine D-2and D-3 receptor signaling in Chinese hamster ovary cells", PSYCHOPHAR, 150(4), 2000, pp. 383-390

Abstract

Rationale: Central dopamine D-2 receptor blockade is an essential propertyof antipsychotic agents in the treatment of schizophrenia. However, for certain of the newer antipsychotics (e.g., sertindole), the in vitro D-2 receptor binding affinity does not correlate with in vivo central dopamine antagonism. Objective: This study aimed to investigate the effect and potency of haloperidol, pipamperone, clozapine, risperidone, sertindole, zotepine, olanzapine, and quetiapine on signaling pathways of human dopamine D-2S and D-3 receptors expressed in Chinese hamster ovary cells and to relate this to their dopamine antagonist potency in vivo. Methods: Chinese hamster ovarycells, stably expressing high levels of hD(2S) and hD(3) receptors were cultured; dopamine-stimulated [S-35]-GTP gamma S binding was investigated in cell membrane preparations, and forskolin-induced cAMP formation was measured in intact cells. Results: The antipsychotic agents inhibited dopamine-stimulated [S-35]-GTP gamma S binding mediated by hot, and hD(3) receptors with potencies equal to their receptor binding affinities. The antipsychoticsreversed dopamine inhibition of cAMP formation (equally well detectable with both hD(2S) and hD(3) receptors) dose dependently at both receptors. Partial agonist effects were not observed with any of the antipsychotics. Antagonistic potencies of haloperidol, risperidone, and pipamperone in the cAMPtest were equal to their receptor binding affinities. Sertindole and olanzapine were more than ten times less potent dopamine antagonists in the intact cell assay than in the assay using cell membranes; the other compounds showed less marked potency differences. Conclusions: Olanzapine and sertindole were less efficacious dopamine antagonists in intact cell assays, possibly due to avid uptake in cells. For sertindole, the weak hot, receptor antagonism in intact cells corresponded to a weak in vivo central dopamine antagonism assessed in rats. However, for olanzapine, hD(2S) receptor binding affinity correlated better with its in vivo dopamine antagonist potency. Such discrepancies may be further explained by relative differences of the compounds in penetrating into the brain.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 18:49:15