5-HT1B/1D受体激动剂对偏头痛患者的血管影响

Vascular effects of 5-HT1B/1D-receptor agonists in patients with migraine headaches.

作者信息

de Hoon J N, Willigers J M, Troost J, Struijker-Boudier H A, Van Bortel L M

机构信息

Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, The Netherlands.

出版信息

Clin Pharmacol Ther. 2000 Oct;68(4):418-26. doi: 10.1067/mcp.2000.110502.

DOI:10.1067/mcp.2000.110502

PMID:11061582

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.

摘要

目的

第二代曲坦类药物被认为比舒马曲坦具有更少的心血管效应。通过比较等效治疗剂量的选择性5-HT1B/1D受体激动剂的血管效应，在体内对此进行了研究。

方法

16例偏头痛患者完成了一项双盲、安慰剂对照、四交叉研究。在口服舒马曲坦（50mg）、利扎曲坦（10mg）、佐米曲坦（2.5mg）或安慰剂1.5小时后，使用超声和压平眼压计测量颈总动脉、肱动脉和颞动脉的动脉血管壁特性、血流和压力波形。在肱动脉处，评估血流诱导的血管舒张（一种内皮依赖性过程），并记录血压。

结果

安慰剂组平均动脉压为91±2mmHg，服用每种曲坦类药物后平均动脉压升高（P<0.05）4%至6%。每种活性治疗均使肱动脉和颈动脉直径减小（P<0.001）。安慰剂组肱动脉等压顺应性为0.077±0.010mm2/kPa，服用舒马曲坦、利扎曲坦和佐米曲坦后分别降低（P<0.01）11%±8%、11%±11%和23%±7%。安慰剂组颈动脉等压顺应性为1.31±0.10mm2/kPa（无变化）。佐米曲坦是唯一能显著减小颞动脉直径的曲坦类药物（减小12%±3%，P<0.001）。服用舒马曲坦（升高26%±11%，P<0.05）和佐米曲坦（升高40%±9%，P=0.001）后，颞动脉血管床阻力增加。血流诱导的血管舒张未受影响。