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在离体灌注和通气的豚鼠肺中,与特布他林相比,福莫特罗和沙美特罗的作用时间都更长。

Formoterol and salmeterol are both long acting compared to terbutaline in the isolated perfused and ventilated guinea-pig lung.

作者信息

Jeppsson A B, Nilsson E, Waldeck B

机构信息

Department of Pharmacology 2, Astra Draco AB, Lund, Sweden.

出版信息

Eur J Pharmacol. 1994 May 12;257(1-2):137-43. doi: 10.1016/0014-2999(94)90705-6.

Abstract

An isolated, perfused and ventilated guinea-pig lung was used to compare the duration of effect of the bronchodilating beta 2-adrenoceptor agonists formoterol, salmeterol and terbutaline. Lung conductance was measured real time with the aid of a computer. Bronchoconstriction was induced in the preparation every 10 min by bolus injections of acetylcholine into the pulmonary artery. Lung conductance was reduced by about 70% after acetylcholine. The test compounds or the vehicle was administered for 1 min as aerosols generated from solutions: formoterol (10 mumol/l), salmeterol (100 mumol/l) and terbutaline (1000 mumol/l). This treatment inhibited the response to acetylcholine by 50-60% within the first 10 min for all three test compounds. The onset of action appeared to be slower for salmeterol than for formoterol and terbutaline. The inhibitory effect of terbutaline disappeared completely during the next 20 min of continuous perfusion (single pass), while both formoterol and salmeterol displayed a significant inhibitory effect 40 min after their administration. Formoterol, when inhaled at a higher dose (100 mumol/l), caused a 90% inhibition of the response to acetylcholine. This effect was completely reversed by 0.1 mumol/l propranolol in the perfusion medium. There were in general no major changes in the basal conductance measured between the acetylcholine provocations.

摘要

使用离体、灌注和通气的豚鼠肺来比较支气管扩张β2肾上腺素能激动剂福莫特罗、沙美特罗和特布他林的作用持续时间。借助计算机实时测量肺传导率。每隔10分钟通过向肺动脉推注乙酰胆碱在该制剂中诱导支气管收缩。乙酰胆碱作用后肺传导率降低约70%。将受试化合物或赋形剂以溶液产生的气雾剂形式给药1分钟:福莫特罗(10 μmol/l)、沙美特罗(100 μmol/l)和特布他林(1000 μmol/l)。对于所有三种受试化合物,这种处理在最初10分钟内将对乙酰胆碱的反应抑制了50 - 60%。沙美特罗的起效似乎比特布他林和福莫特罗慢。在接下来连续灌注(单次通过)的20分钟内,特布他林的抑制作用完全消失,而福莫特罗和沙美特罗在给药40分钟后仍显示出显著的抑制作用。当以较高剂量(100 μmol/l)吸入时,福莫特罗对乙酰胆碱反应的抑制率达90%。灌注介质中0.1 μmol/l的普萘洛尔可完全逆转这种作用。在乙酰胆碱激发试验之间测量的基础传导率总体上没有重大变化。

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