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Titolo:
A PHARMACOLOGICAL PROFILE OF THE SELECTIVE SILENT 5-HT1A RECEPTOR ANTAGONIST, WAY-100635
Autore:
FORSTER EA; CLIFFE IA; BILL DJ; DOVER GM; JONES D; REILLY Y; FLETCHER A;
Indirizzi:
WYETH RES UK LTD,DEPT NEUROPHARMACOL,HUNTERCOMBE LANE S MAIDENHEAD SL6 0PH BERKS ENGLAND WYETH RES UK LTD,DEPT NEUROPHARMACOL MAIDENHEAD SL6 0PH BERKS ENGLAND WYETH RES UK LTD,DEPT MOLEC PHARMACOL MAIDENHEAD SL6 0PH BERKS ENGLAND WYETH RES UK LTD,DEPT MED CHEM MAIDENHEAD SL6 0PH BERKS ENGLAND WYETH AYERST RES,CENT NERVOUS SYST PHARMACOL PRINCETON NJ 08540
Titolo Testata:
European journal of pharmacology
fascicolo: 1, volume: 281, anno: 1995,
pagine: 81 - 88
SICI:
0014-2999(1995)281:1<81:APPOTS>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSTSYNAPTIC 5-HT(1A) RECEPTORS; SEROTONIN RECEPTOR; EXPRESSION; LIGANDS; NEURONS; CLONING;
Keywords:
5-HT1A RECEPTOR; WAY-100635; 5-HT1A RECEPTOR ANTAGONIST;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
E.A. Forster et al., "A PHARMACOLOGICAL PROFILE OF THE SELECTIVE SILENT 5-HT1A RECEPTOR ANTAGONIST, WAY-100635", European journal of pharmacology, 281(1), 1995, pp. 81-88

Abstract

WAY-100635 inyl]ethyl]N-2-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride) is an achiral phenylpiperazine derivative that binds with high affinity and selectivity to the 5-HT1A receptor. WAY-100635 displaced specific binding of the 5-HT1A radioligand, [H-3]8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) to rat hippocampal membranes with a pIC(50) of 8.87. This represented a greater than 100-fold selectivity relative to binding at other 5-HT receptor subtypes and major neurotransmitter receptor, reuptake and ion channel sites. In functional assays, WAY-100635 was a potent 5-HT1A receptor antagonist, with no evidence of any 5-HT1A receptor agonist or partial agonist activity. In the isolated guinea-pig ileum WAY-100635 was a potent and, at high concentrations, an insurmountable antagonist of the 5-HT1A receptor agonist action of 5-carboxamidotryptamine, with an apparent pA(2) value (at 0.3 nM) of 9.71. WAY-100635 blocked the inhibitory action of 8-OH-DPAT on dorsal raphe neuronal firing in the anaesthetised rat at doses which had no inhibitory action per se. In behavioural models, WAY-100635 itself induced no overt behavioural changes but potently antagonised the behavioural syndrome induced by 8-OH-DPAT in the rat and guinea-pig (minimum effective dose = 0.003 mg/kg s.c, and ID50 = 0.01 mg/kg s.c., respectively). WAY-100635 also blocked the hypothermia induced by 8-OH-DPAT in the mouse and rat with ID50 values of 0.01 mg/kg s.c. These data indicate that WAY-100635 will be used as a standard antagonist in further studies of 5-HT1A receptor function.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 19:42:38