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Titolo:
SB-272183, a selective 5-HT1A, 5-HT1B and 5-HT1D receptor antagonist in native tissue
Autore:
Watson, J; Roberts, C; Scott, C; Kendall, I; Collin, L; Day, NC; Harries, MH; Soffin, E; Davies, CH; Randall, AD; Heightman, T; Gaster, L; Wyman, P; Parker, C; Price, GW; Middlemiss, DN;
Indirizzi:
GlaxoSmithKline, Neurosci Res, Harlow CM19 5AW, Essex, England GlaxoSmithKline Harlow Essex England CM19 5AW ow CM19 5AW, Essex, England GlaxoSmithKline, Dept Med Chem, Harlow CM19 5AW, Essex, England GlaxoSmithKline Harlow Essex England CM19 5AW ow CM19 5AW, Essex, England Pharmagene PLC, Royston SG8 5HD, Herts, England Pharmagene PLC Royston Herts England SG8 5HD ston SG8 5HD, Herts, England
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 6, volume: 133, anno: 2001,
pagine: 797 - 806
SICI:
0007-1188(200107)133:6<797:SAS55A>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
DORSAL RAPHE NUCLEUS; RAT-BRAIN; IN-VITRO; TERMINAL AUTORECEPTOR; SEROTONERGIC NEURONS; INTRINSIC ACTIVITY; MESSENGER-RNA; WAY-100635; GR127935; AGONIST;
Keywords:
SB-272183; 5-HT1A; 5-HT1B; 5-HT1D receptors; recombinant cells; human; guinea-pig; rat;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Watson, J GlaxoSmithKline, Neurosci Res, New Frontiers Sci Pk,3rd Ave, Harlow CM19 5AW, Essex, England GlaxoSmithKline New Frontiers Sci Pk,3rd Ave Harlow Essex England CM19 5AW
Citazione:
J. Watson et al., "SB-272183, a selective 5-HT1A, 5-HT1B and 5-HT1D receptor antagonist in native tissue", BR J PHARM, 133(6), 2001, pp. 797-806

Abstract

1 A novel compound, SE-272183 (5-Chloro-2, 3-dihydro-6-[4-methylpiperazin-1-yl]-1[4-pyridin-4-yl]napth-1-ylaminocarbonyl]-1H-indole), has been shown to have high affinity for human 5-HT1A, 5-HT1B and 5-HT1D receptors with pK(i) values of 8.0, 8.1 and 8.7 respectively and is at least 30 fold selective over a range of other receptors.2 [S-35]-GTP gammaS binding studies showed that SE-272183 acts as a partial agonist at human recombinant 5-HT1A, 5-HT1B and 5-HT1D receptors with intrinsic activities of 0.4, 0.4 and 0.8 respectively, compared to 5-HT. SE-272183 inhibited 5-HT-induced stimulation of [S-35]-GTP gammaS binding at human 5-HT1A and 5-HT1B receptors to give pA(2) values of 8.2 and 8.5 respectively. However, from [S-35]-GTP gammaS autoradiographic studies in rat and human dorsal raphe nucleus, SB-272183 did not display intrinsic activity up to 10 muM but did block 5-HT-induced stimulation of [S-35]-GTP gammaS binding.3 From electrophysiological studies in rat raphe slices in vitro, SE-272183 did not effect cell firing rate up to 1 muM but was able to attenuate (+)8-OH-DPAT-induced inhibition of cell firing to give an apparent pK(b) of 7.1.4 SE-272183 potentiated electrically-stimulated [H-3]-5-HT release from rat and guinea-pig cortical slices at 100 and 1000 nM, similar to results previously obtained with the 5-HT1B and 5-HT1D receptor antagonist, GR127935.5 Fast cyclic voltammetry studies in rat dorsal raphe nucleus showed that SE-272183 could block sumatriptan-induced inhibition of 5-HT efflux, with an apparent pK(b) of 7.2, but did not effect basal efflux up to 1 muM.6 These studies show that, in vitro, SE-272183 acts as an antagonist at native tissue 5-HT1A, 5-HT1B and 5-HT1D receptors.

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Documento generato il 20/09/20 alle ore 03:26:40