Pharmacodynamics and Drug Action
Clinical Pharmacology & Therapeutics (2000) 68, 418–426; doi: 10.1067/mcp.2000.110502
Vascular effects of 5-HT1B/1D-receptor agonists in patients with migraine headaches*
Jan N. J. M. de Hoon MD1, Jean M. Willigers BSc1, Jaap Troost MD1, Harry A. J. Struijker-Boudier PhD1 and Luc M. A. B. Van Bortel MD1
1Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, the Department of Biophysics, Maastricht University, and the Department of Neurology, University Hospital of Maastricht, Maastricht, Netherlands
Correspondence: Luc M. A. B. Van Bortel, MD, Maastricht University, Cardiovascular Research Institute Maastricht, Department of Pharmacology and Toxicology, PO Box 616, 6200 MD Maastricht, The Netherlands
*Supported by AstraZeneca, Zoetermeer, The Netherlands.
Received 22 May 2000; Accepted 24 July 2000.
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.)
