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Titolo:
PHARMACOLOGICAL PROFILE OF T-0201, A HIGHLY POTENT AND ORALLY-ACTIVE ENDOTHELIN RECEPTOR ANTAGONIST
Autore:
HOSHINO T; YAMAUCHI R; KIKKAWA K; YABANA H; MURATA S;
Indirizzi:
TANABE SEIYAKU CO LTD,LEAD OPTIMIZAT RES LAB,2-2-50 KAWAGISHI TODA SAITAMA 3358505 JAPAN
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 2, volume: 286, anno: 1998,
pagine: 643 - 649
SICI:
0022-3565(1998)286:2<643:PPOTAH>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
RABBIT PULMONARY-ARTERY; CHRONIC HEART-FAILURE; VASOCONSTRICTOR PEPTIDE; BOSENTAN; CLONING; CONTRACTION; HYPERTROPHY; EXPRESSION; INHIBITION; CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
T. Hoshino et al., "PHARMACOLOGICAL PROFILE OF T-0201, A HIGHLY POTENT AND ORALLY-ACTIVE ENDOTHELIN RECEPTOR ANTAGONIST", The Journal of pharmacology and experimental therapeutics, 286(2), 1998, pp. 643-649

Abstract

The authors studied the pharmacological properties of N-(6-(2-(5-bromopyrimidin-4-yl)-4-(2-hydroxy-1, 1-dimethylethyl)benzensulfonamide sodium salt sesquihydrate (T-0201), a new nonpeptide endothelin (ET) receptor antagonist, in vitro and in vivo. In binding studies, T-0201 competitively antagonized the specific binding of [I-125]-ET-1 to human cloned ET,receptors (the K-l value was 0.015 +/- 0.004 nM). T-0201 weakly inhibited [(125)]-ET-1-binding to human cloned ETB receptors; the K-l value was 41 +/- 21 nM. T-0201 shifted the concentration-response curve of ET-I-induced contraction of the isolated rat aorta (ET, receptors) to the right (pA(2) = 9.0 +/- 0.2). In the isolated rat trachea, aselective ETB agonist sarafotoxin S6c-induced contraction was inhibited by T-0201 (pA(2) = 6.8 +/- 0.3). T-0201 also caused the inhibition of ET-I-induced contraction of the isolated rabbit pulmonary artery (pA(2) = 5.7 +/- 0.3). in anesthetized rats, T-0201 (0.01-1 mg/kgj inhibited the presser response to exogenous big ET-1 (1 nmol/kg i.v.), after both i.v. and p.o. administration, in a dose-dependent manner. The significant inhibitory effect of orally administered T-0201 on big ET-1-induced presser response lasted for 4 hr at 0.1 mg/kg and for 8 hr at1 mg/kg. Thus the present study demonstrates that T-0201 is a highly potent, long-lasting, orally active and selective ETB receptor antagonist.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/04/20 alle ore 08:24:04