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

Autor:	Saracheva KE; Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Medical University of Plovdiv, Plovdiv, Bulgaria., Prissadova NA; Department of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv., Turiiski VI; Department of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv., Slavchev VI; Department of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv., Krastev AD; Department of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv., Getova DP; Laboratory of Neuropharmacology, Technological Center for Emergency Medicine (TCEMED), Plovdiv.
Jazyk:	angličtina
Zdroj:	Folia medica [Folia Med (Plovdiv)] 2017 Mar 01; Vol. 59 (1), pp. 31-36.
DOI:	10.1515/folmed-2017-0006
Abstrakt:	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.
Databáze:	MEDLINE
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