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几种药物溶剂的药效学活性研究。3. 1,2 - 丙二醇、四氢糠醇 - 聚乙二醇醚(THFP)、聚氧乙烯山梨醇酐单油酸酯(PSM)

[Studies on the parmacodynamic activity of several drug solvents. 3. 1,2-Propanediol, tetrahydrofurfuryl alcohol-polyethylene glycol ether (THFP), olyoxyethylene sorbitan monooleate (PSM)].

作者信息

Budden R, Kühl U G, Buschmann G

出版信息

Arzneimittelforschung. 1978;28(9):1586-93.

PMID:582560
Abstract

The drug solvents 1,2-propanediol, tetrahydrofurfuryl alcohol polyethylene glycolether (THFP, Tetraglycol), and polyoxyethylene sorbitan monooleate (PSM, Tween 80) were examined for their pharmacodynamic properties in the following tests: i.p. toxicity, "sign pattern", inclined screen test, balance rod test, and potentiation of hexobarbitone sleeping time in mice, spasmolytic activity in the guinea pig isolated ileum, and cardiovascular studies in anaesthetized rats, cats, and dogs including the i.v. toxicity. The solvents showed only small differences in their toxicity in the mouse and rat; PSM, however, was more toxic than 1,2-propanediol and THFP in the cat and dogs. The latter solvent, on the other hand, was the most potent in inducing behavioural changes and in potentiating hexobarbitone sleeping time. In the isolated ileum the solvents showed different spasmolytic potencies, depending on whether histamine, carbachol or BaCl2 was used as a spasmogen. The spasmolytic activity of 1,2-propanediol and THFP is classified as unspecific, whereas PSM seemed to have a specific anticholinergic pattern in the isolated ileum. After i.v. administration in rats, cats, and dogs the solvents caused cardiovascular effects even in very low doses. Based on the pharmacodynamic properties, doses are recommended for each solvent which should not be exceeded without control experiments in the laboratory routine. These tolerable doses do not only depend on the species but also on the test concerned.

摘要

在以下试验中对药物溶剂1,2 - 丙二醇、四氢糠醇聚乙二醇醚(THFP,四甘醇)和聚氧乙烯山梨醇酐单油酸酯(PSM,吐温80)的药效学特性进行了研究:小鼠腹腔注射毒性、“体征模式”、倾斜筛板试验、平衡杆试验、戊巴比妥睡眠时间的增强试验、豚鼠离体回肠的解痉活性以及对麻醉大鼠、猫和狗的心血管研究,包括静脉注射毒性试验。这些溶剂在小鼠和大鼠中的毒性仅显示出微小差异;然而,在猫和狗中,PSM的毒性比1,2 - 丙二醇和THFP更大。另一方面,后一种溶剂在诱导行为变化和增强戊巴比妥睡眠时间方面最为有效。在离体回肠中,根据使用组胺、卡巴胆碱或氯化钡作为致痉剂的不同,这些溶剂表现出不同的解痉效力。1,2 - 丙二醇和THFP的解痉活性被归类为非特异性的,而PSM在离体回肠中似乎具有特定的抗胆碱能模式。在大鼠、猫和狗中静脉注射后,这些溶剂即使在非常低的剂量下也会引起心血管效应。根据药效学特性,针对每种溶剂推荐了剂量,在实验室常规操作中若无对照实验,不应超过这些剂量。这些耐受剂量不仅取决于物种,还取决于相关试验。

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