神经激肽-1受体拮抗剂R116301抑制P物质诱导的静脉扩张。

Neurokinin-1 receptor antagonist R116301 inhibits substance P-induced venodilation.

作者信息

Romerio S C, Linder L, Haefeli W E

机构信息

Department of Internal Medicine, University Hospital, Basel, Switzerland.

出版信息

Clin Pharmacol Ther. 1999 Nov;66(5):522-7. doi: 10.1016/S0009-9236(99)70016-0.

DOI:10.1016/S0009-9236(99)70016-0

PMID:10579480

Abstract

OBJECTIVE

To test the effect of the neurokinin-1 receptor antagonist hydroxybutanedioate (R116301) in human hand veins in vivo.

METHODS

In a randomized, double-blind, placebo-controlled crossover study we used the hand vein compliance method to evaluate the inhibition of the response to substance P by R116301.

RESULTS

In hand veins preconstricted with phenylephrine to 21% +/- 2.6% (mean +/- SEM, placebo) and 25% +/- 3.0% (R116301) of the initial diameter, substance P resulted in a mean venodilation of 84% +/- 7% and 87% +/- 13% (P = .8) before administration of placebo and R116301, respectively. Oral administration of 300 mg R116301 resulted in peak plasma concentrations of 1.16 +/- 0.1 microg/mL within 128 +/- 14 minutes. With increasing R116301 plasma concentrations, substance P-induced venodilation decreased significantly (P < .001), whereas placebo had no effect. Mean substance P-induced venodilation was markedly reduced to 8% +/- 7%.

CONCLUSION

This study confirms the presence of neurokinin-1 receptors in human veins and the effectiveness of the neurokinin-1 receptor antagonist R116301 in human hand veins.

摘要

目的

在体内测试神经激肽-1受体拮抗剂羟基丁二酸酯（R116301）对人手部静脉的作用。

方法

在一项随机、双盲、安慰剂对照的交叉研究中，我们采用手部静脉顺应性方法评估R116301对P物质反应的抑制作用。

结果

在用去氧肾上腺素将手部静脉预收缩至初始直径的21%±2.6%（平均值±标准误，安慰剂组）和25%±3.0%（R116301组）后，在给予安慰剂和R116301之前，P物质分别导致平均静脉扩张84%±7%和87%±13%（P = 0.8）。口服300 mg R116301后，在128±14分钟内血浆浓度峰值达到1.16±0.1 μg/mL。随着R116301血浆浓度升高，P物质诱导的静脉扩张显著降低（P < 0.001），而安慰剂无作用。P物质诱导的平均静脉扩张显著降至8%±7%。