Effects of the Novel High-affinity 5-HT(1B/1D)-receptor Ligand Frovatriptan on the Rat Carotid Artery

Kremena E. Saracheva 1 , 2 , Natalia A. Prissadova 3 , Valentin I. Turiiski 3 , Valeri I. Slavchev 3 , Atanas D. Krastev 3  and Damianka P. Getova 4
  • 1 Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Medical University of Plovdiv, Plovdiv, Bulgaria Bulgaria
  • 2 Department of Pharmacology and Medical Toxicology, Faculty of Pharmacy, Medical University of Plovdiv, 15A Vassil Aprilov Blvd., 4002 Plovdiv, Bulgaria
  • 3 Department of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv, Bulgaria
  • 4 Laboratory of Neuropharmacology, Technological Center for Emergency Medicine (TCEMED), Plovdiv, Bulgaria

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.

Aim: 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.

Conclusion: 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.

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