title: Effects of the Novel High-affinity 5-HT(1B/1D)-receptor Ligand Frovatriptan on the Rat Carotid Artery.
abstract: BACKGROUND
  In blood vessels 5-HT stimulates sympathetic nerves, the endothelium and vascular smooth muscle cells. Triptans are specific anti-migraine drugs and they activate the serotoninergic 5HT1b/d receptors causing vasoconstriction of the cerebral vessels.
  
  
  OBJECTIVE
  To evaluate the effect of frovatriptan on isolated rat carotid artery.
  
  
  METHODS
  Contractile activity of the preparations was registered isometrically. Krebs solution (pH = 7.4) was used for washing smooth muscle (SM) preparations aerated with 95% O2 and 5% CO2 at 37°C. The 60-minute adaptation of tone level of preparations was taken as a starting tone and the changes such as contraction or relaxation were calculated using it.
  
  
  RESULTS
  Frovatriptan (1×10-6 mol/l - 1×10-5 mol/l) induced a contraction, but at higher concentrations it caused relaxation of the carotid artery. The L-norepinephrine contractile reaction was enhanced in the presence of frovatriptan. In the presence of 5-HT2 receptor antagonist, methysergide, frovatriptan increased the relaxation. In the presence of the specific α-1 receptor antagonist, prazosin, the frovatriptan-induced relaxation decreased.
  
  
  CONCLUSIONS
  The observed contractile effect of frovatriptan is probably associated with the main effect of the drug - activation of the serotoninergic 5HT1B /1D receptors causing vasoconstriction of the cerebral vessels and their anti-migraine effect. At higher concentrations, frovatriptan, most likely via some non-specific mechanism, could activate the following intracellular chain reaction: stimulation of α1D could activate eNOS which may increase in the concentration of NO which results in the final effect of relaxation.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Medical University of Plovdiv, Plovdiv, Bulgaria.
authors.forename: Kremena E
authors.initials: KE
authors.lastname: Saracheva
authors.affiliation: Department of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Prissadova
authors.affiliation: Department of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv.
authors.forename: Valentin I
authors.initials: VI
authors.lastname: Turiiski
authors.affiliation: Department of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv.
authors.forename: Valeri I
authors.initials: VI
authors.lastname: Slavchev
authors.affiliation: Department of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv.
authors.forename: Atanas D
authors.initials: AD
authors.lastname: Krastev
authors.affiliation: Laboratory of Neuropharmacology, Technological Center for Emergency Medicine (TCEMED), Plovdiv.
authors.forename: Damianka P
authors.initials: DP
authors.lastname: Getova
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D002227:Carbazoles; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D058825:Serotonin 5-HT1 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D014363:Tryptamines; C108128:frovatriptan; D011224:Prazosin; D008784:Methysergide
keywords: carotid artery; frovatriptan; migraine; serotonin; triptans