Abstract
Background
Initial concerns about the coronary side-effect potential of the anti-migraine drug sumatriptan and second-generation triptans initiated cranioselectivity studies using proximal human coronary arteries. However, myocardial ischaemia may originate from both large and small human coronary arteries.
Methods
We investigated the contractions to sumatriptan in proximal (internal diameter 2–3 mm), distal (internal diameter 1,000–1,500 μm) and small (internal diameter 500–1,000 μm) human epicardial coronary arteries and compared these with contractions in the human middle meningeal artery. Concentration response curves to sumatriptan in human coronary arteries were constructed in the absence or presence of the 5-hydroxytryptamine1B (5-HT1B) receptor antagonist SB224289 and the 5-HT1D receptor antagonist BRL15572. The effect of sumatriptan on increased cyclic adenosine monophosphate (cAMP) levels induced by forskolin in proximal and distal coronary artery segments was investigated using a biochemical assay. Western blotting was used to analyse the 5-HT1B receptor density in the human arteries.
Results
Contractions in the proximal human coronary artery were significantly smaller than those in the human meningeal artery, as we showed previously. In contrast, contractions to sumatriptan in distal and small human coronary arteries were not different from those in the human meningeal artery. The 5-HT1B receptor antagonist SB224289, but not the 5-HT1D receptor antagonist BRL15572, inhibited the contraction induced by sumatriptan in the coronary arteries. Moreover, in distal, but not in proximal, coronary arteries, sumatriptan inhibited the increase in cAMP levels induced by forskolin. Contrary to our expectations, the 5-HT1B receptor expression was more pronounced in the proximal human coronary artery than in the distal and small human coronary artery.
Conclusions
Based on functional experiments in distal and small human coronary arteries, contractions to sumatriptan are not as cranioselective as previously assumed. However, the vast clinical experience with sumatriptan and other triptans has proven that these drugs are cardiovascularly safe when contraindications are taken into account.
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Acknowledgments
This study was supported by a research grant from the Netherlands Organisation for Scientific Research (NWO Vidi Grant 917.11.349 to AMVDB). We thank Dr X. Lu for his help with the Western blot experiments.
Conflicts of interest
KYC, SL, MBR, RV, IMG, AHJD, CMV, AB, CC and AMVDB have no conflicts of interest, have full control of all primary data and agree to allow the journal to review their data if requested.
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Chan, K.Y., Labruijere, S., Ramírez Rosas, M.B. et al. Cranioselectivity of Sumatriptan Revisited: Pronounced Contractions to Sumatriptan in Small Human Isolated Coronary Artery. CNS Drugs 28, 273–278 (2014). https://doi.org/10.1007/s40263-013-0136-0
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DOI: https://doi.org/10.1007/s40263-013-0136-0