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作用于5-羟色胺受体和α1-肾上腺素能受体的药物,是否比仅作用于α1-肾上腺素能受体的药物有更强的降压作用?

Are drugs that act both on serotonin receptors and alpha 1-adrenoceptors more potent hypotensive agents than those that act only on alpha 1-adrenoceptors?

作者信息

Ramage A G

机构信息

Academic Department of Pharmacology, Royal Free Hospital School of Medicine, Hampstead, London, U.K.

出版信息

J Cardiovasc Pharmacol. 1988;11 Suppl 1:S30-4.

PMID:2459511
Abstract

Simultaneous recordings of cardiac, splanchnic, and renal nerve activity, blood pressure, heart rate, and femoral arterial conductance were made in anaesthetised paralysed cats. Cumulative dose-response curves were constructed for either cinanserin or 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in animals that had received a maximal hypotensive dose of prazosin that had, in addition to decreasing blood pressure, decreased heart rate and background activity in all three nerves. Cinanserin failed to further affect these parameters. However, 8-OH-DPAT caused further falls in blood pressure and heart rate and virtually abolished the remaining activity in all nerves. Part of the extra decrease in heart rate was shown to be due to an increase in vagal tone. It was concluded that if a drug has both an agonist action at the putative 5-HT1A receptors and an antagonist action at alpha 1-adrenoceptors, it is a more potent hypotensive agent than if it only blocks alpha 1-adrenoceptors. These observations do not support a role for 5-HT2 receptors in the maintenance of blood pressure.

摘要

在麻醉致瘫的猫身上同时记录心脏、内脏和肾神经活动、血压、心率以及股动脉传导率。对已接受最大降压剂量哌唑嗪的动物,绘制西那色林或8-羟基-2-(二正丙基氨基)四氢萘(8-OH-DPAT)的累积剂量-反应曲线。哌唑嗪除降低血压外,还降低心率以及所有三条神经的背景活动。西那色林未能进一步影响这些参数。然而,8-OH-DPAT导致血压和心率进一步下降,几乎消除了所有神经的剩余活动。部分额外的心率下降被证明是由于迷走神经张力增加所致。得出的结论是,如果一种药物在假定的5-HT1A受体上既有激动作用,又在α1-肾上腺素受体上有拮抗作用,那么它作为降压药比仅阻断α1-肾上腺素受体的药物更有效。这些观察结果不支持5-HT2受体在维持血压方面发挥作用。

相似文献

1
Are drugs that act both on serotonin receptors and alpha 1-adrenoceptors more potent hypotensive agents than those that act only on alpha 1-adrenoceptors?作用于5-羟色胺受体和α1-肾上腺素能受体的药物,是否比仅作用于α1-肾上腺素能受体的药物有更强的降压作用?
J Cardiovasc Pharmacol. 1988;11 Suppl 1:S30-4.
2
Evidence that 5-HT2 receptors mediate the pressor effect of 8-OH-DPAT in the spinally pithed rat.5-羟色胺2受体介导8-羟基二丙胺四乙酸对脊髓毁损大鼠的升压作用的证据。
Arch Int Pharmacodyn Ther. 1990 Jul-Aug;306:114-29.
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An investigation of the effects of intravenous injection of the 5-hydroxytryptamine 2 receptor antagonists ketanserin and LY 53857 on blood pressure in anesthetized spontaneously hypertensive rats.静脉注射5-羟色胺2受体拮抗剂酮色林和LY 53857对麻醉的自发性高血压大鼠血压影响的研究。
J Pharmacol Exp Ther. 1989 Feb;248(2):736-40.
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Comparison of the effects of IVth ventricular administration of some tryptamine analogues with those of 8-OH-DPAT on autonomic outflow in the anaesthetized cat.麻醉猫中第四脑室注射某些色胺类似物与8-羟基二苯丙氨酸对自主神经传出的影响比较。
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Interaction of urapidil with brain serotonin-1A receptors increases the blood pressure reduction due to peripheral alpha-adrenoceptor inhibition.乌拉地尔与脑血清素-1A受体的相互作用,因外周α-肾上腺素能受体抑制作用而增强了降压效果。
J Hypertens Suppl. 1988 Dec;6(2):S65-8.
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5-HT1A and alpha-2 adrenergic receptors mediate the hyperglycemic and hypoinsulinemic effects of 8-hydroxy-2-(di-n-propylamino)tetralin in the conscious rat.5-羟色胺1A受体和α-2肾上腺素能受体介导了8-羟基-2-(二正丙基氨基)四氢萘对清醒大鼠的高血糖和低胰岛素血症作用。
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Ventrolateral medulla: an important site of action for the hypotensive effect of drugs that activate serotonin-1A receptors.
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10
Evidence that the putative 5-HT1A receptor agonists, 8-OH-DPAT and ipsapirone, have a central hypotensive action that differs from that of clonidine in anaesthetised cats.有证据表明,假定的5-羟色胺1A受体激动剂8-羟基二苯丙氨酸(8-OH-DPAT)和ipsapirone在麻醉猫中具有与可乐定不同的中枢性降压作用。
Eur J Pharmacol. 1987 Jun 19;138(2):179-91. doi: 10.1016/0014-2999(87)90431-6.

引用本文的文献

1
Clinical pharmacokinetics of vasodilators. Part II.血管扩张剂的临床药代动力学。第二部分。
Clin Pharmacokinet. 1998 Jul;35(1):9-36. doi: 10.2165/00003088-199835010-00002.
2
Evidence that different regional sympathetic outflows vary in their sensitivity to the sympathoinhibitory actions of putative 5-HT1A and alpha 2-adrenoceptor agonists in anaesthetized cats.有证据表明,在麻醉猫中,不同区域的交感神经输出对假定的5-HT1A和α2-肾上腺素能受体激动剂的交感抑制作用的敏感性存在差异。
Br J Pharmacol. 1989 Dec;98(4):1157-64. doi: 10.1111/j.1476-5381.1989.tb12660.x.
3
Subclassification of alpha 1-adrenoceptor recognition sites by urapidil derivatives and other selective antagonists.
用乌拉地尔衍生物及其他选择性拮抗剂对α1-肾上腺素能受体识别位点进行亚分类
Br J Pharmacol. 1989 Jul;97(3):691-700. doi: 10.1111/j.1476-5381.1989.tb12005.x.
4
The mechanism of the sympathoinhibitory action of urapidil: role of 5-HT1A receptors.乌拉地尔交感神经抑制作用的机制:5-羟色胺1A受体的作用
Br J Pharmacol. 1991 Apr;102(4):998-1002. doi: 10.1111/j.1476-5381.1991.tb12290.x.