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

Abstract

Citation: Saracheva KE, Prissadova NA, Turiiski VI, Slavchev VI, Krastev AD, Getova DP. Effects of the novel high-affi nity 5-HT(1B/1D)-receptor ligand frovatriptan on the rat carotid artery.Folia Medica 2017;59(1): 31-36. doi: 10.1515/folmed-2017-0006 Background: In blood vessels 5-HT stimulates sympathetic nerves, the endothelium and vascular smooth muscle cells. Triptans are specifi c anti-migraine drugs and they activate the serotoninergic 5HT1b/d receptors causing vasoconstriction of the cerebral vessels. Aim: To evaluate the eff ect 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% O 2 and 5% CO 2 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 specifi c α-1 receptor antagonist, prazosin, the frovatriptan-induced relaxation decreased. Conclusion:The observed contractile eff ect of frovatriptan is probably associated with the main eff ect of the drug -activation of the serotoninergic 5HT 1B /1D receptors causing vasoconstriction of the cerebral vessels and their anti-migraine eff ect. At higher concentrations, frovatriptan, most likely via some non-specifi c mechanism, could activate the following intracellular chain reaction: stimulation of α 1D could activate eNOS which may increase in the concentration of NO which results in the fi nal eff ect of relaxation. BACKGROUND

Duality in response of intracranial vessels to nitroglycerin revealed in rats by imaging photoplethysmography

“…On the other hand, there are observations that sumatriptan did not exhibit constricting properties in relation to the porcine isolated meningeal artery 75 . Moreover, even a dilating effect on various cranial arteries was shown ex vivo and in vivo for triptans that indicates the selectivity, dose dependence, and species specificity of their vascular action, for example, in relation to humans and rodents 68 , 76 – 78 . As for the above-mentioned "vascular" effects of the NTG and sumatriptan interaction, they also cannot be called unambiguous.…”

Study on in Vivo Pial Vessels Alterations and Activity of Isolated Vascular Smooth Muscles in Abdominal Hypertension Rats

“…28,29 Our previous studies have manifested leading role of 5-HT 1В receptors in vasoconstriction of isolated rat arteria carotis communis. 30 There is evidence that 5-HT excitatory effect on rabbit arteria carotis communisis mediated by 5-HT 2А receptors, while potentiated reactivity of arterial vessels to 5-HT is done by autosensetization through 5-HT 1В receptors. 31 The above considerations could be accepted as explanation of the contribution of increased contractility of arteria carotis communis, as well as causal-effect relation between lowered brain perfusion and SM sensitization to 5-HT.…”