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.
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Authors | Fabrice Barbe, Etienne Gautier, Jean-Pierre Bidouard, Alain Grosset, Stephen E O'Connor, Philip Janiak |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 474
Issue 1
Pg. 117-20
(Aug 01 2003)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 12909202
(Publication Type: Journal Article)
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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
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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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