The Potential Anti-Migraine Compound SB-220453 does not Contract Human Isolated Blood Vessels or Myocardium; A Comparison with Sumatriptan

The mechanistically novel benzopyran derivative SB-220453, which is undergoing clinical evaluation in migraine, exhibits a high affinity for a selective, but not yet characterized, binding site in the human brain. It inhibits nitric oxide release and cerebral vasodilatation following cortical spreading depression as well as carotid vasodilatation induced by trigeminal nerve stimulation in the cat. The aim of our study was to investigate the contractile properties of SB-220453 on a number of human isolated blood vessels (coronary artery, saphenous vein and middle meningeal artery) as well as atrial and ventricular cardiac trabeculae. While sumatriptan induced marked contractions in three blood vessels investigated, SB-220453 was devoid of any effect. In atrial and ventricular cardiac trabeculae, neither SB-220453 nor sumatriptan displayed a positive or negative inotropic effect. Since SB-220453 did not contract the middle meningeal artery, we conclude that potential anti-migraine effects are not mediated via a direct cerebral vasoconstriction. The lack of activity of SB-220453 in coronary artery, saphenous vein and cardiac trabeculae demonstrates that the compound is unlikely to cause adverse cardiac side-effects.

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Dihydroergotamine and sumatriptan in isolated human coronary artery, middle meningeal artery and saphenous vein

Cephalalgia ◽

10.1177/0333102414544977 ◽

2014 ◽

Vol 35 (2) ◽

pp. 182-189 ◽

Cited By ~ 9

Author(s):

Sieneke Labruijere ◽

Kayi Y Chan ◽

René de Vries ◽

Antoon J van den Bogaerdt ◽

Clemens M Dirven ◽

...

Keyword(s):

Cardiovascular Disease ◽

Coronary Artery ◽

Coronary Arteries ◽

Saphenous Vein ◽

Middle Meningeal Artery ◽

Human Coronary Artery ◽

Response Curves ◽

Meningeal Arteries ◽

Proximal Coronary Artery ◽

Meningeal Artery

Background Dihydroergotamine (DHE) and sumatriptan are contraindicated in patients with cardiovascular disease because of their vasoconstricting properties, which have originally been explored in proximal coronary arteries. Our aim was to investigate DHE and sumatriptan in the proximal and distal coronary artery, middle meningeal artery and saphenous vein. Methods Blood vessel segments were mounted in organ baths and concentration response curves for DHE and sumatriptan were constructed. Results In the proximal coronary artery, meningeal artery and saphenous vein, maximal contractions to DHE (proximal: 8 ± 4%; meningeal: 32 ± 7%; saphenous: 52 ± 11%) and sumatriptan (proximal: 17 ± 7%; meningeal: 61 ± 18%, saphenous: 37 ± 8%) were not significantly different. In the distal coronary artery, contractions to DHE (5 ± 2%) were significantly smaller than those to sumatriptan (17 ± 9%). At clinically relevant concentrations, mean contractions to DHE and sumatriptan were below 3% in proximal coronary arteries and below 6% in distal coronary arteries. Contractions in the meningeal artery and saphenous vein were higher (7%–38%). Conclusions Contractions to DHE in distal coronary arteries are smaller than those to sumatriptan, while at clinical concentrations they both induce only slight contractions. In meningeal arteries contractions to DHE and sumatriptan are significantly larger, showing their cranioselectivity. Contractions to DHE in the saphenous vein are higher than those in the arteries, confirming its venous contractile properties.

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Characterization of Sumatriptan-Induced Contractions in Human Isolated Blood Vessels Using Selective 5-HT1B and 5-HT1D Receptor Antagonists and In Situ Hybridization

Cephalalgia ◽

10.1046/j.1468-2982.2002.00295.x ◽

2002 ◽

Vol 22 (2) ◽

pp. 83-93 ◽

Cited By ~ 31

Author(s):

RWM van den Broek ◽

P Bhalla ◽

A MaassenVanDenBrink ◽

R de Vries ◽

HS Sharma ◽

...

Keyword(s):

In Situ Hybridization ◽

Coronary Artery ◽

Blood Vessels ◽

Saphenous Vein ◽

Peripheral Blood ◽

Temporal Artery ◽

Middle Meningeal Artery ◽

Response Curves ◽

Temporal Arteries

The 5-HT1B/1D receptor agonist sumatriptan is effective in aborting acute attacks of migraine and is known to cause constriction of cranial arteries as well as some peripheral blood vessels. The present study set out to investigate whether 5-HT1B and/or 5-HT1D receptors mediate contractions of the human isolated middle meningeal and temporal arteries (models for anti-migraine efficacy) and coronary artery and saphenous vein (models for side-effect potential). Concentration-response curves were made with sumatriptan (1 nM-100 μM) in blood vessels in the absence or presence of selective antagonists at 5-HT1B (SB224289) and 5-HT1D (BRL15572) receptors. SB224289 antagonized sumatriptan-induced contractions in all blood vessels, although the antagonism profile was different amongst these blood vessels. In the temporal artery, SB224289 abolished contraction to sumatriptan, whereas in the middle meningeal artery and saphenous vein sumatriptan-induced contractions were blocked in an insurmountable fashion. Moreover, SB224289 acted as a weak surmountable antagonist in the coronary artery (pKB: 6.4 ± 0.2). In contrast, BRL15572 had little or no effect on sumatriptan-induced contractions in the four blood vessels investigated. In situ hybridization revealed the expression of 5-HT1B receptor mRNA in the smooth muscle as well as endothelial cells of the blood vessels, whereas the mRNA for the 5-HT1D receptor was only very weakly expressed. These results show that the 5-HT1B receptor is primarily involved in sumatriptan-induced contractions of human cranial as well as peripheral blood vessels.

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Effects of two isometheptene enantiomers in isolated human blood vessels and rat middle meningeal artery – potential antimigraine efficacy

The Journal of Headache and Pain ◽

10.1186/s10194-019-1003-2 ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Alejandro Labastida-Ramírez ◽

Eloísa Rubio-Beltrán ◽

Kristian A. Haanes ◽

René de Vries ◽

Ruben Dammers ◽

...

Keyword(s):

Blood Vessels ◽

Human Blood ◽

Middle Meningeal Artery ◽

Meningeal Artery

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Middle meningeal artery embolization for the management of chronic subdural hematoma

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2019-014730 ◽

2019 ◽

Vol 11 (9) ◽

pp. 912-915 ◽

Cited By ~ 16

Author(s):

David Fiorella ◽

Adam S Arthur

Keyword(s):

Minimally Invasive ◽

Blood Vessels ◽

Subdural Hematoma ◽

Potential Role ◽

Chronic Subdural Hematoma ◽

Middle Meningeal Artery ◽

Endovascular Management ◽

Artery Embolization ◽

Conventional Management ◽

Meningeal Artery

Chronic subdural hematoma (cSDH) is one of the most common neurosurgical diagnoses in adults. The disease is fundamentally a disorder of the meningeal blood vessels, and options exist for the minimally invasive neuroendovascular management. We review the potential role for the endovascular management of cSDH within the context of a discussion of the epidemiology, pathophysiology, and conventional management of this disease.

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Differences in Expression of Genes Involved in Bone Development and Morphogenesis in the Walls of Internal Thoracic Artery and Saphenous Vein Conduits May Provide Markers Useful for Evaluation Graft Patency

International Journal of Molecular Sciences ◽

10.3390/ijms20194890 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4890

Author(s):

Mariusz J. Nawrocki ◽

Bartłomiej Perek ◽

Patrycja Sujka-Kordowska ◽

Aneta Konwerska ◽

Sandra Kałużna ◽

...

Keyword(s):

Coronary Artery ◽

Blood Vessels ◽

Saphenous Vein ◽

Internal Thoracic Artery ◽

Bone Development ◽

Quantitative Polymerase Chain Reaction ◽

Expression Patterns ◽

Graft Patency ◽

Basic Knowledge ◽

Valuable Insight

Coronary artery bypass grafting (CABG) is one of the most efficient procedures for patients with advanced coronary artery disease. From all the blood vessels with the potential to be used in this procedure, the internal thoracic artery (ITA) and the saphenous vein (SV) are the most commonly applied as aortocoronary conduits. Nevertheless, in order to evaluate the graft patency and efficiency effectively, basic knowledge should be constantly expanding at the molecular level as well, as the understanding of predictive factors is still limited. In this study, we have employed the expressive microarray approach, validated with Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), to analyze the transcriptome of both venous and arterial grafts. Searching for potential molecular factors, we analyzed differentially expressed gene ontologies involved in bone development and morphogenesis, for the possibility of discovery of new markers for the evaluation of ITA and SV segment quality. Among three ontological groups of interest—“endochondral bone morphogenesis”, “ossification”, and “skeletal system development”—we found six genes common to all of them. BMP6, SHOX2, COL13A1, CSGALNACT1, RUNX2, and STC1 showed differential expression patterns in both analyzed vessels. STC1 and COL13A1 were upregulated in ITA samples, whereas others were upregulated in SV. With regard to the Runx2 protein function in osteogenic phenotype regulation, the RUNX2 gene seems to be of paramount importance in assessing the potential of ITA, SV, and other vessels used in the CABG procedure. Overall, the presented study provided valuable insight into the molecular background of conduit characterization, and thus indicated genes that may be the target of subsequent studies, also at the protein level. Moreover, it has been suggested that RUNX2 may be recognized as a molecular marker of osteogenic changes in human blood vessels.

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