SL65.0472在犬后肢缺血模型中可阻断5-羟色胺诱导的血管收缩。

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

作者信息

Barbe Fabrice, Gautier Etienne, Bidouard Jean-Pierre, Grosset Alain, O'Connor Stephen E, Janiak Philip

机构信息

Sanofi-Synthélabo Research, Cardiovascular Thrombosis Research Department, 1 Avenue Pierre Brossolette, 91380 Chilly-Mazarin, France.

出版信息

Eur J Pharmacol. 2003 Aug 1;474(1):117-20. doi: 10.1016/s0014-2999(03)02032-6.

DOI:10.1016/s0014-2999(03)02032-6

PMID:12909202

Abstract

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-HT1B/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 microg/kg i.v.), but unaffected by ketanserin (300 microg/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.

摘要

我们研究了5-羟色胺（5-HT）5-HT1B/5-HT2A受体拮抗剂SL65.0472（7-氟-2-氧代-4-[2-[4-(噻吩并[3,2-c]吡啶-4-基)哌嗪-1-基]乙基]-1,2-二氢喹啉-1-乙酰胺）在犬后肢缺血模型中拮抗5-HT和舒马曲坦血管收缩作用的能力。犬接受右髂外动脉结扎和右股浅动脉切除，导致右后肢灌注减少（-31%，P<0.05）。在用L-精氨酸甲酯、酚妥拉明和普萘洛尔预处理后，主动脉内注射5-HT显著降低了右缺血后肢的血流量（-50±2%，P<0.05）。SL65.0472（300μg/kg静脉注射）可显著抑制5-HT诱导的血管收缩（-66%，P<0.05），但5-HT2A受体拮抗剂酮色林（300μg/kg静脉注射）对其无影响。SL65.0472还可阻断舒马曲坦在缺血和正常灌注后肢诱导的血管收缩。因此，SL65.0472是5-HT受体介导的后肢血管收缩的有效拮抗剂。