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强效降钙素基因相关肽受体拮抗剂,telcagepant,不会影响健康男性中硝化甘油引起的血管舒张。

The potent calcitonin gene-related peptide receptor antagonist, telcagepant, does not affect nitroglycerin-induced vasodilation in healthy men.

机构信息

Center for Clinical Pharmacology, University Hospital Gasthuisberg (K.U. Leuven), Leuven, Belgium.

出版信息

Br J Clin Pharmacol. 2011 May;71(5):708-17. doi: 10.1111/j.1365-2125.2010.03869.x.

Abstract

AIMS

To assess the effect of the calcitonin gene-related peptide (CGRP) receptor antagonist, telcagepant, on the haemodynamic response to sublingual nitroglycerin (NTG).

METHODS

Twenty-two healthy male volunteers participated in a randomized, placebo-controlled, double-blind, two-period, crossover study. Subjects received 500 mg telcagepant or placebo followed, 1.5 h later, by 0.4 mg NTG. To assess the haemodynamic response the following vascular parameters were measured: blood pressure, aortic augmentation index (AIx) and brachial artery diameter (BAD). Data are presented as mean (95% confidence interval, CI).

RESULTS

The aortic AIx following NTG decreased by -18.50 (-21.02, -15.98) % after telcagepant vs. -17.28 (-19.80, -14.76) % after placebo. The BAD fold increase following NTG was 1.14 (1.12, 1.17) after telcagepant vs. 1.13 (1.10, 1.15) after placebo. For both AIx and BAD, the hypothesis that telcagepant does not significantly affect the changes induced by NTG is supported (P < 0.0001). In addition, no vasoconstrictor effect of telcagepant could be demonstrated.

CONCLUSIONS

Telcagepant did not affect NTG-induced haemodynamic changes. These data suggest that NTG-induced vasodilation is not CGRP dependent.

摘要

目的

评估降钙素基因相关肽(CGRP)受体拮抗剂 telcagepant 对舌下硝酸甘油(NTG)引起的血流动力学反应的影响。

方法

22 名健康男性志愿者参加了一项随机、安慰剂对照、双盲、两周期、交叉研究。受试者先接受 500mg telcagepant 或安慰剂,1.5 小时后舌下给予 0.4mg NTG。为了评估血流动力学反应,测量了以下血管参数:血压、主动脉增强指数(AIx)和肱动脉直径(BAD)。数据以平均值(95%置信区间,CI)表示。

结果

与安慰剂相比,telcagepant 后 NTG 引起的主动脉 AIx 下降了-18.50(-21.02,-15.98)%,而安慰剂后下降了-17.28(-19.80,-14.76)%。与安慰剂相比,telcagepant 后 NTG 引起的 BAD 折叠增加了 1.14(1.12,1.17)%,而安慰剂后增加了 1.13(1.10,1.15)%。对于 AIx 和 BAD,telcagepant 不显著影响 NTG 诱导的变化的假设得到支持(P<0.0001)。此外,telcagepant 没有显示出血管收缩作用。

结论

telcagepant 不影响 NTG 诱导的血流动力学变化。这些数据表明,NTG 诱导的血管舒张不依赖于 CGRP。

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