WAY 405，一种对血管α（1）-肾上腺素能受体亲和力低的新型5-羟色胺（1A）受体拮抗剂。

WAY 405, a new silent 5-HT (1A) receptor antagonist with low affinity for vascular alpha (1)-adrenoceptors.

作者信息

Villalobos-Molina R, Orozco-Méndez M, López-Guerrero J J, Gallardo-Ortíz I A

机构信息

Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados-Sede Sur, México City.

出版信息

Auton Autacoid Pharmacol. 2005 Oct;25(4):185-9. doi: 10.1111/j.1474-8673.2005.00350.x.

DOI:10.1111/j.1474-8673.2005.00350.x

PMID:16176451

Abstract

1 The effect of WAY 405 ((R)-N-(2-methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexane carboxamide), a putative 5-HT(1A) receptor antagonist, on cardiovascular function was studied. 2 In anaesthetized rats, the i.v. injection of WAY 405 did not significantly modify basal heart rate nor blood pressure at doses of 1, 3, 10 and 30 microg kg(-1); while the antagonist dose dependently antagonized the 5-HT(1A) receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin)-induced hypotension and bradycardia. 3 WAY 405 antagonized noradrenaline-induced contraction in isolated arteries, with pK(B) values of 6.6+/-0.1, 6.5+/-0.1 and 6.5+/-0.1, for rat tail artery (alpha(1A)-adrenoceptors), rabbit aorta (alpha(1B)-adrenoceptors), and rat aorta (alpha(1D)-adrenoceptors) respectively. 4 The results show that in the control of blood pressure the new compound, WAY 405, behaves as a silent 5-HT(1A) receptor antagonist in the anaesthetized rat, also having low affinity for vascular alpha(1)-adrenoceptors.

摘要

1 研究了一种假定的5-HT(1A)受体拮抗剂WAY 405（(R)-N-(2-甲基-(4-吲哚基-1-哌嗪基)乙基)-N-(2-吡啶基)环己烷甲酰胺）对心血管功能的影响。2 在麻醉大鼠中，静脉注射WAY 405，剂量为1、3、10和30微克/千克时，对基础心率和血压无显著影响；而该拮抗剂剂量依赖性地拮抗5-HT(1A)受体激动剂8-OH-DPAT（8-羟基-2-(二正丙基氨基)四氢萘）诱导的低血压和心动过缓。3 WAY 405拮抗去甲肾上腺素诱导的离体动脉收缩，对大鼠尾动脉（α(1A)-肾上腺素能受体）、兔主动脉（α(1B)-肾上腺素能受体）和大鼠主动脉（α(1D)-肾上腺素能受体）的pK(B)值分别为6.6±0.1、6.5±0.1和6.5±0.1。4 结果表明，在血压控制方面，新化合物WAY 405在麻醉大鼠中表现为沉默的5-HT(1A)受体拮抗剂，对血管α(1)-肾上腺素能受体也具有低亲和力。