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Titolo:
SB-224289 - A NOVEL SELECTIVE (HUMAN) 5-HT1B RECEPTOR ANTAGONIST WITHNEGATIVE INTRINSIC ACTIVITY
Autore:
SELKIRK JV; SCOTT C; HO M; BURTON MJ; WATSON J; GASTER LM; COLLIN L; JONES BJ; MIDDLEMISS DN; PRICE GW;
Indirizzi:
SMITHKLINE BEECHAM PHARMACEUT,DEPT NEUROSCI,NEW FRONTIERS SCI PK HARLOW CM19 5AW ESSEX ENGLAND SMITHKLINE BEECHAM PHARMACEUT,DEPT NEUROSCI HARLOW CM19 5AW ESSEX ENGLAND SMITHKLINE BEECHAM PHARMACEUT,DEPT MED CHEM HARLOW CM19 5AW ESSEX ENGLAND
Titolo Testata:
British Journal of Pharmacology
fascicolo: 1, volume: 125, anno: 1998,
pagine: 202 - 208
SICI:
0007-1188(1998)125:1<202:S-ANS(>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOMBINANT HUMAN 5-HT1D-ALPHA; GUINEA-PIG; PHARMACOLOGICAL CHARACTERIZATION; TERMINAL AUTORECEPTOR; CONSTITUTIVE ACTIVITY; H5-HT1D RECEPTORS; INHIBITION; SUBTYPES; CLASSIFICATION; SEROTONIN;
Keywords:
5-HT; SB-224289; 5-HT1B AUTORECEPTOR; INVERSE AGONIST;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
23
Recensione:
Indirizzi per estratti:
Citazione:
J.V. Selkirk et al., "SB-224289 - A NOVEL SELECTIVE (HUMAN) 5-HT1B RECEPTOR ANTAGONIST WITHNEGATIVE INTRINSIC ACTIVITY", British Journal of Pharmacology, 125(1), 1998, pp. 202-208

Abstract

1 Human 5-HT1B (h(5)-HT1B) and human 5-HT1D (h(5)-HT1D) receptors show remarkably similar pharmacology with few compounds discriminating the receptors. We report here on a novel compound, SE-224289 diazol-3-yl)biphenyl-4-yl]carbonyl]2,3,6,7-tetra-, hydrospiro [furo [2,3-f]indole-3,4'-piperidine] oxalate), which has high affinity for h5-HT1B receptors (pK(1) = 8.16 +/- 0.06) and displays over 75 fold selectivity for the h(5)-HT1B receptor over all other 5-HT receptors including the h5-HT1D receptor and all other receptors tested thus far. 2 Functional activity of SE-224289 was measured in a [S-35]GTP gamma S binding assay on recombinant h5-HT1B and h5-HT1D receptors expressed in Chinese Hamster Ovary (CHO) cells. SE-224289 displayed negative intrinsic activityat both receptors with higher potency at h5-HT1B receptors. SB-224289caused a rightward shift of agonist concentration response curves consistent with competitive antagonism and generated affinities comparable with those obtained from competition radioligand receptor binding studies. 3 SB-224289 potentiated [H-3]5-HT release from electrically stimulated guinea-pig cerebral cortical slices to the same extent as as the non-selective 5-HT1 antagonist methiothepin. SE-234289 also fully reversed the inhibitory effect of exogenously superfused 5-HT on electrically stimulated release. 4 Using SE-224289 as a tool compound, we confirm that in guinea-pig cerebral cortex the terminal 5-HT autoreceptor is of the 5-HT1B subtype.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/10/20 alle ore 21:02:18