BRL-46470 POTENTLY ANTAGONIZES NEURAL RESPONSES ACTIVATED BY 5-HT(3) RECEPTORS

被引：43

作者：

NEWBERRY, NR ^{[1
]}

WATKINS, CJ ^{[1
]}

SPROSEN, TS ^{[1
]}

BLACKBURN, TP ^{[1
]}

GRAHAMESMITH, DG ^{[1
]}

LESLIE, RA ^{[1
]}

机构：

[1] SMITHKLINE BEECHAM PHARMACEUT,HARLOW,ESSEX,ENGLAND

来源：

NEUROPHARMACOLOGY | 1993年 / 32卷 / 08期

关键词：

5-HT; SEROTONIN; VAGUS; NEUROBLASTOMA CELL; 5-HT(3) RECEPTORS; BRL-46470;

D O I：

10.1016/0028-3908(93)90180-B

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The effect of a novel 5-HT3 receptor antagonist, BRL 46470, has been studied on two electrophysiological models for 5-HT3 receptors: grease-gap recordings from rat isolated vagus nerve and whole-cell patch-clamp recordings from mouse neuroblastoma-rat glioma NG108-15 cells. Its action on the rat vagus nerve was compared to that of four other 5-HT3 receptor antagonists. On the rat vagus, BRL 46470 reduced the maximum depolarizing response to 5-HT in a concentration-dependent manner with an IC50 of 0.3-1.0 nM, but the EC50 for 5-HT was not appreciably affected. This action was similar to that of granisetron and ICS 205-930, but differed from that of GR38032F and (+)-tubocurarine which produced clear rightward shifts of the concentration-response curve to 5-HT. The 5-HT-induced fast inward current of voltage-clamped NG108-15 cells was also antagonized by 1 nM BRL 46470 in an insurmountable manner. In contrast to (+)-tubocurarine, the action of BRL 46470 on the mt vagus nerve and NG108-15 cells did not readily reverse on washing with antagonist-free medium. It is concluded that BRL 46470 is a potent, insurmountable 5-HT3 receptor antagonist on the rat vagus and NG108-15 cells.

引用

页码：729 / 735

页数：7

共 32 条

[1] BRL-46470A - A HIGHLY POTENT, SELECTIVE AND LONG-ACTING 5-HT(3) RECEPTOR ANTAGONIST WITH ANXIOLYTIC-LIKE PROPERTIES [J].