SL65.0472 blocks 5-hydroxytryptamine-induced vasoconstriction in a dog hindlimb ischemia model |
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Authors: | Barbe Fabrice Gautier Etienne Bidouard Jean-Pierre Grosset Alain O'Connor Stephen E Janiak Philip |
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Institution: | Sanofi-Synthélabo Research, Cardiovascular Thrombosis Research Department, 1 Avenue Pierre Brossolette, 91380 Chilly-Mazarin, France. |
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Abstract: | We have studied the ability of SL65.0472 (7-fluoro-2-oxo-4-2-4-(thieno3,2-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. |
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Keywords: | 5-HT receptor Sumatriptan Vasoconstriction Hindlimb ischemia SL65 0472 Ketanserin |
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