Cranioselectivity of Sumatriptan Revisited: Pronounced Contractions to Sumatriptan in Small Human Isolated Coronary Artery

Chan, Kayi Y.; Labruijere, Sieneke; Ramírez‐Rosas, Martha B.; Vries, René de; Garrelds, Ingrid M.; Danser, A.H. Jan; Villalón, Carlos M.; Bogaerdt, Antoon van den; Dirven, Clemens; MaassenVanDenBrink, Antoinette

doi:10.1007/s40263-013-0136-0

Cited by 13 publications

(17 citation statements)

References 14 publications

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“…This allowed us to compare the results from the current study with results obtained earlier. In accordance with our previous work (Chan et al, ), sumatriptan induced a concentration‐dependent contraction in human isolated coronary arteries, which tended to be larger in distal than in proximal coronary artery segments. This contraction was apparent at clinically relevant concentrations and is most likely due to activation of 5‐HT 1B receptors in vascular smooth muscle (Chan et al, ).…”

Section: Discussionsupporting

confidence: 93%

“…In accordance with our previous work (Chan et al, ), sumatriptan induced a concentration‐dependent contraction in human isolated coronary arteries, which tended to be larger in distal than in proximal coronary artery segments. This contraction was apparent at clinically relevant concentrations and is most likely due to activation of 5‐HT 1B receptors in vascular smooth muscle (Chan et al, ). In contrast, lasmiditan did not induce a contraction at concentrations up to 100 μM (≥100× the clinically relevant concentrations) in either proximal or distal coronary arteries.…”

Section: Discussionsupporting

confidence: 93%

“…After further washout, a concentration–response curve to vehicle, sumatriptan, or lasmiditan was constructed, using whole logarithmic steps from 1 nM up to 10 μM. After finishing the curve and washing several times until reaching equilibrium, the functional integrity of the endothelium was verified by observing relaxation to substance P (10 nM; coronary and meningeal arteries) or bradykinin (1 μM; mammary arteries), after precontraction with the TxA 2 analogue U46619 (10–100 nM; Chan et al, ; Labruijere et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…Currently, the specific therapies for acute antimigraine treatment are the triptans, selective 5‐HT 1B / 1D receptor agonists that also display varying levels of 5‐HT 1F receptor affinity. Unfortunately, not all patients respond to triptans (Diener & Limmroth, ), and they are contraindicated in patients with cardiovascular disease, due to their contractile properties via activation of 5‐HT 1B receptors in coronary arteries (Chan et al, ; Dodick et al, ; Labruijere et al, ; MaassenVanDenBrink, Reekers, Bax, Ferrari, & Saxena, ). Therefore, there is a need for novel antimigraine drugs for the patients that do not respond to the current available treatments, but also, for those patients with cardiovascular disease.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of binding, functional activity, and contractile responses of the selective 5‐HT_1F receptor agonist lasmiditan

Rubio‐Beltrán¹,

Labastida-Ramírez²,

Haanes³

et al. 2019

British J Pharmacology

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Background and Purpose:Triptans are 5-HT 1B/1D receptor agonists (that also display 5-HT 1F receptor affinity) with antimigraine action, contraindicated in patients with coronary artery disease due to their vasoconstrictor properties. Conversely, lasmiditan was developed as an antimigraine 5-HT 1F receptor agonist. To assess the selectivity and cardiovascular effects of lasmiditan, we investigated the binding, functional activity, and in vitro/in vivo vascular effects of lasmiditan and compared it to sumatriptan.Experimental Approach: Binding and second messenger activity assays of lasmiditan and other serotoninergic agonists were performed for human 5-HT 1A , 5-HT 1B , 5-HT 1D , 5-ht 1E , 5-HT 1F , 5-HT 2A , 5-HT 2B , and 5-HT 7 receptors, and the results were correlated with their potency to constrict isolated human coronary arteries (HCAs). Furthermore, concentration-response curves to lasmiditan and sumatriptan were performed in proximal and distal HCA, internal mammary, and middle meningeal arteries. Finally, anaesthetized female beagle dogs received i.v. infusions of lasmiditan or sumatriptan in escalating cumulative doses, and carotid and coronary artery diameters were measured.Key Results: Lasmiditan showed high selectivity for 5-HT 1F receptors. Moreover, the functional potency of the analysed compounds to inhibit cAMP increase through 5-HT 1B receptor activation positively correlated with their potency to contract HCA.In isolated human arteries, sumatriptan, but not lasmiditan, induced contractions.Likewise, in vivo, sumatriptan decreased coronary and carotid artery diameters at clinically relevant doses, while lasmiditan was devoid of vasoconstrictor activity at all doses tested. ---This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Conclusions and Implications:Lasmiditan is a selective 5-HT 1F receptor agonist devoid of vasoconstrictor activity. This may represent a cardiovascular safety advantage when compared to the triptans. SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Rubio-Beltrán E, Labastida-Ramírez A, Haanes KA, et al. Characterization of binding, functional activity, and contractile responses of the selective 5-HT 1F receptor agonist lasmiditan. Br J Pharmacol. 2019; https://doi.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Characterization of binding, functional activity, and contractile responses of the selective 5‐HT_1F receptor agonist lasmiditan

Rubio‐Beltrán¹,

Labastida-Ramírez²,

Haanes³

et al. 2019

British J Pharmacology

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“…4,5 The triptans are among a number of migraine treatments that have a vasoconstrictive mechanism of action. 6 There are sparse case reports in the literature describing different ischaemic side effects of this drug group. 5,[7][8][9][10][11][12][13] We report three cases where third nerve paresis developed in patients who were treated with oral sumatriptan for recurrent nonophthalmoplegic migraine.…”

Section: Introductionmentioning

confidence: 99%

Triptans and third nerve paresis: a case series of three patients

Novitskaya

Cates

Bowes

et al. 2016

Eye

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Purpose The aim of this report is to increase awareness of a possible association between cranial nerve paresis and the use of sumatriptan in migraine sufferers, particularly in patients who have additional vascular risk factors. Patients and methods We describe a series of three cases where third nerve paresis developed in patients who were treated with the oral form of sumatriptan. All of the patients had a clear history of repetitive migraine headache and none of them had previous third nerve paresis. Conclusion Among a variety of medications for the treatment of migraine, there are some drugs with vasoconstrictive effects, particularly triptans. These drugs may be a contributing factor for microvascular damage of the cranial nerves and other organs.

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Beyond its anti‐migraine properties, sumatriptan is an anti‐inflammatory agent: A systematic review

Ala

Ghasemi

Jafari

et al. 2021

Drug Development Research

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Sumatriptan is the first available medication from triptans family that was approved by the U.S. Food and Drug Administration for migraine attacks and cluster headaches in 1991. Most of its action is mediated by selective 5‐HT1B/1D receptor agonism. Recent investigations raised the possibility of repositioning of this drug to other indications beyond migraine, as increasing evidence suggests for an anti‐inflammatory property of sumatriptan. We performed a literature search using PubMed, Web of Science, Scopus, and Google Scholar using “inflammation AND sumatriptan” or “inflammation AND 5HT1B/D” as the keywords. Then, articles were screened for their relevance and those directly discussing the correlation between inflammation and sumatriptan or 5HT1B/D were included. Total references reviewed or inclusion/exclusion were 340 retrieved full‐text articles (n = 340), then based on critical assessment 66 of them were included in this systematic review. Our literature review indicates that at low doses, sumatriptan can reduce inflammatory markers (e.g., interleukin‐1β, tumor necrosis factor‐α, and nuclear factor‐κB), affects caspases and changes cells lifespan. Additionally, nitric oxide synthase and nitric oxide signaling seem to be regulated by this drug. It also inhibits the release of calcitonin gene‐related peptide. Sumatriptan protects against many inflammatory conditions including cardiac and mesenteric ischemia/reperfusion, skin flap, pruritus, peripheral, and central nervous system injuries such as spinal cord injury, testicular torsion‐detorsion, oral mucositis, and other experimental models. Considering the safety and potency of low dose sumatriptan compared to corticosteroids and other immunosuppressive medications, it is worth to take advantage of sumatriptan in inflammatory conditions.

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Cranioselectivity of Sumatriptan Revisited: Pronounced Contractions to Sumatriptan in Small Human Isolated Coronary Artery

Cited by 13 publications

References 14 publications

Characterization of binding, functional activity, and contractile responses of the selective 5‐HT_1F receptor agonist lasmiditan

Characterization of binding, functional activity, and contractile responses of the selective 5‐HT_1F receptor agonist lasmiditan

Triptans and third nerve paresis: a case series of three patients

Beyond its anti‐migraine properties, sumatriptan is an anti‐inflammatory agent: A systematic review

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Cranioselectivity of Sumatriptan Revisited: Pronounced Contractions to Sumatriptan in Small Human Isolated Coronary Artery

Cited by 13 publications

References 14 publications

Characterization of binding, functional activity, and contractile responses of the selective 5‐HT1F receptor agonist lasmiditan

Characterization of binding, functional activity, and contractile responses of the selective 5‐HT1F receptor agonist lasmiditan

Triptans and third nerve paresis: a case series of three patients

Beyond its anti‐migraine properties, sumatriptan is an anti‐inflammatory agent: A systematic review

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Product

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Characterization of binding, functional activity, and contractile responses of the selective 5‐HT_1F receptor agonist lasmiditan

Characterization of binding, functional activity, and contractile responses of the selective 5‐HT_1F receptor agonist lasmiditan