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

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.
AuthorsFabrice Barbe, Etienne Gautier, Jean-Pierre Bidouard, Alain Grosset, Stephen E O'Connor, Philip Janiak
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 474 Issue 1 Pg. 117-20 (Aug 01 2003) ISSN: 0014-2999 [Print] Netherlands
PMID12909202 (Publication Type: Journal Article)
Chemical References
  • 7-fluoro-2-oxo-4-(2-(4-(thieno(3,2-c)pyridin-4-yl)piperazin-1-yl)ethyl)-1,2-dihydroquinoline-1-acetamide
  • Piperazines
  • Quinolines
  • Serotonin Antagonists
  • Serotonin
  • NG-Nitroarginine Methyl Ester
Topics
  • Animals
  • Disease Models, Animal
  • Dogs
  • Hindlimb (blood supply)
  • Ischemia (metabolism, physiopathology)
  • Male
  • NG-Nitroarginine Methyl Ester (administration & dosage)
  • Piperazines (pharmacology)
  • Quinolines (pharmacology)
  • Regional Blood Flow (drug effects)
  • Serotonin (administration & dosage, metabolism)
  • Serotonin Antagonists (pharmacology)
  • Vasoconstriction (drug effects)

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