5-HT antagonism on cerebral and common carotid arteries by the 5-HT uptake inhibitors femoxetine and paroxetine.
The 5-hydroxytryptamine (5-HT) antagonism of methysergide was compared with that of the phenylpiperidine 5-HT uptake inhibitors, paroxetine and femoxetine, using two different models; the isolated cat middle cerebral artery and the common carotid artery of pithed rat perfused with the rat's own blood (autoperfusion). The extracorporeal circulation consisted of about 1.5 ml blood, which was temperature regulated to 36-38 degrees at the inlet to the carotid vessel by an automatic thermistor coupled heating system. In these experiments systemic blood pressure responses and perfusion pressure responses to 5-HT were recorded simultaneously. The 5-HT induced contractile response of the middle cerebral artery was reduced in a noncompetitive way by both uptake inhibitors at concentrations above 0.3 microM which is about 100 times the concentration needed for methysergide. In autoperfusion experiments inhibition was observed only at 5 mg/kg of both drugs. However, methysergide 0.001 mg/kg totally abolished all 5-HT responses. The uptake inhibitors can therefore be described as weak 5-HT antagonists.
D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects; D002536:Cerebral Arteries / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004148:Dioxolanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010477:Perfusion; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000840:Anisoles; D004148:Dioxolanes; D010880:Piperidines; D012702:Serotonin Antagonists; D012701:Serotonin; D008784:Methysergide