Vascular effects of 5-HT-receptor agonists in patients with migraine headaches

Clinical Pharmacology & TherapeuticsVolume 68, Issue 4 p. 418-426 Pharmacodynamics and Drug Action Vascular effects of 5-HT1B/1D-receptor agonists in patients with migraine headaches Jan N. J. M. de Hoon MD, Jan N. J. M. de Hoon MD Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, the Department of Biophysics, Maastricht University, and the Department of Neurology, University Hospital of Maastricht, Maastricht, NetherlandsSearch for more papers by this authorJean M. Willigers BSc, Jean M. Willigers BSc Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, the Department of Biophysics, Maastricht University, and the Department of Neurology, University Hospital of Maastricht, Maastricht, NetherlandsSearch for more papers by this authorJaap Troost MD, Jaap Troost MD Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, the Department of Biophysics, Maastricht University, and the Department of Neurology, University Hospital of Maastricht, Maastricht, NetherlandsSearch for more papers by this authorHarry A. J. Struijker-Boudier PhD, Harry A. J. Struijker-Boudier PhD Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, the Department of Biophysics, Maastricht University, and the Department of Neurology, University Hospital of Maastricht, Maastricht, NetherlandsSearch for more papers by this authorLuc M. A. B. van Bortel MD, Corresponding Author Luc M. A. B. van Bortel MD Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, the Department of Biophysics, Maastricht University, and the Department of Neurology, University Hospital of Maastricht, Maastricht, NetherlandsMaastricht University, Cardiovascular Research Institute Maastricht, Department of Pharmacology and Toxicology, PO Box 616, 6200 MD Maastricht, The NetherlandsSearch for more papers by this author Jan N. J. M. de Hoon MD, Jan N. J. M. de Hoon MD Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, the Department of Biophysics, Maastricht University, and the Department of Neurology, University Hospital of Maastricht, Maastricht, NetherlandsSearch for more papers by this authorJean M. Willigers BSc, Jean M. Willigers BSc Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, the Department of Biophysics, Maastricht University, and the Department of Neurology, University Hospital of Maastricht, Maastricht, NetherlandsSearch for more papers by this authorJaap Troost MD, Jaap Troost MD Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, the Department of Biophysics, Maastricht University, and the Department of Neurology, University Hospital of Maastricht, Maastricht, NetherlandsSearch for more papers by this authorHarry A. J. Struijker-Boudier PhD, Harry A. J. Struijker-Boudier PhD Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, the Department of Biophysics, Maastricht University, and the Department of Neurology, University Hospital of Maastricht, Maastricht, NetherlandsSearch for more papers by this authorLuc M. A. B. van Bortel MD, Corresponding Author Luc M. A. B. van Bortel MD Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, the Department of Biophysics, Maastricht University, and the Department of Neurology, University Hospital of Maastricht, Maastricht, NetherlandsMaastricht University, Cardiovascular Research Institute Maastricht, Department of Pharmacology and Toxicology, PO Box 616, 6200 MD Maastricht, The NetherlandsSearch for more papers by this author First published: 29 October 2000 https://doi.org/10.1067/mcp.2000.110502Citations: 11Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Objectives Second-generation triptans are believed to have fewer cardiovascular effects than sumatriptan. This was investigated in vivo by comparing the vascular effects of equipotent therapeutic dosages of selective 5-HT1B/1D-receptor agonists. Methods Sixteen patients with migraine headaches completed a double-blind, placebo-controlled, four-way crossover study. With ultrasonography and applanation tonometry used 1.5 hours after the oral intake of sumatriptan (50 mg), rizatriptan (10 mg), zolmitriptan (2.5 mg), or placebo arterial vessel wall properties, blood flow and pressure waveforms were measured in common carotid, brachial, and temporal arteries. At the brachial artery, flow-induced vasodilation (an endothelium-dependent process) was evaluated, and blood pressures were recorded. Results Mean arterial pressure, 91 ± 2 mm Hg after placebo, increased (P < .05) by 4% to 6% after administration of each triptan. Each active treatment decreased (P < .001) both brachial and carotid artery diameter. Isobaric compliance of the brachial artery, 0.077 ± 0.010 mm2/kPa after placebo, decreased (P < .01) by 11% ± 8%, 11% ± 11%, and 23% ± 7% after administration of sumatriptan, rizatriptan, and zolmitriptan, respectively. Isobaric compliance of the carotid artery was 1.31 ± 0.10 mm2/kPa after placebo (no change). Zolmitriptan was the only triptan that decreased temporal artery diameter significantly (by 12% ± 3%, P < .001). The resistance of the temporal artery vascular bed increased after administration of sumatriptan (by 26% ± 11%, P < .05) and zolmitriptan (by 40% ± 9%, P = .001). Flow-induced vasodilation was unaffected. Conclusions Selective 5-HT1B/1D-receptor agonists induce vasoconstriction and decrease compliance of conduit arteries. These effects are more pronounced at muscular (temporal, brachial) compared with elastic (carotid) arteries. Resistance is only increased at the temporal artery vascular bed, suggesting cranioselectivity for resistance vessels. Endothelial function is not differently affected by any of the triptans tested. (Clin Pharmacol Ther 2000;68:418-26.) Clinical Pharmacology & Therapeutics (2000) 68, 418–426; doi: 10.1067/mcp.2000.110502 Citing Literature Volume68, Issue4October 2000Pages 418-426 RelatedInformation