SL65.0472 blocks 5-hydroxytryptamine-induced vasoconstriction in a dog hindlimb ischemia model

被引：8

作者：

Barbe, F ^{[1
]}

Gautier, E ^{[1
]}

Bidouard, JP ^{[1
]}

Grosset, A ^{[1
]}

O'Connor, SE ^{[1
]}

Janiak, P ^{[1
]}

机构：

[1] Cardiovasc Thrombosis Res Dept, F-91380 Chilly Marazin, France

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2003年 / 474卷 / 01期

关键词：

5-HT receptor; sumatriptan; vasoconstriction; hindlimb ischemia; SL65.0472; ketanserin;

D O I：

10.1016/S0014-2999(03)02032-6

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

We have studied the ability of SL65.0472 (7-fluoro-2-oxo-4-[2-[4-(thieno[3,2 -c]pyridin-4-yl)piperazin-1-yl]ethyl]-1,2-dihydroquinoline-1-acetamide), a 5-hydroxytryptamine (5-HT) 5-HTIB/5-HT2A receptor antagonist, to antagonise the vasoconstrictor effects of 5-HT and sumatriptan in a canine model of hindlimb ischemia. Dogs underwent right external iliac artery ligation and right superficial femoral artery excision, resulting in decreased perfusion (-31%, P<0.05) in the right hindlimb. Following pretreatment with L-NAME, phentolamine and propranolol, intra-aortic injection of 5-HT markedly reduced blood flow to the right ischemic hindlimb (-50 +/- 2%, P<0,05). 5-HT induced vasoconstriction was significantly inhibited (-66%, P<0.05) by SL65.0472 (300 mug/kg i.v.), but unaffected by ketanserin (300 mug/kg i.v.), a 5-HT2A receptor antagonist. SL65.0472 also blocked sumatriptan-induced vasoconstriction in ischemic and normally perfused hindlimbs. Thus, SL65.0472 is an effective antagonist of 5-HT-receptor mediated hindlimb vasoconstriction. (C) 2003 Elsevier B.V. All rights reserved.

引用

页码：117 / 120

页数：4

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