Vick J, Weiss L, Ellis S
Food and Drug Administration, Center for Drug Evaluation and Research, Washington, DC 20204.
Arch Int Pharmacodyn Ther. 1994 Jan-Feb;327(1):13-24.
Phenylpropanolamine is found in a number of over-the-counter preparations commonly used for appetite control or as a cold remedy. Even though widely used, some questions still exist as to its effect on the cardiovascular system of man. Both anesthetized and unanesthetized adult beagle dogs were used in this study. In the unanesthetized conditioned dog, blood pressure and heart rate were measured using an inflatable tail cuff. In the first group, consisting of 12 dogs, phenylpropanolamine was given (0.0, 3.1, 6.25 and 12.5 mg/kg) via a stomach tube and the animals were followed for 300 minutes. Each dose of phenylpropanolamine was given to 4 groups made up of 3 dogs each. It produced dose-dependent increases in blood pressure and decreases of heart rate. Maximum changes were noted at 30 to 60 minutes, lasting for 3 to 5 hours. A second group of 9 unanesthetized dogs was given repeated oral doses of phenylpropanolamine (3 groups of 3 animals each). Doses of 3 mg/kg and 6 mg/kg, given orally, produced approximately the same increase in blood pressure and decrease of heart rate as previously observed. At 6 hours, these same doses of phenylpropanolamine produced little or no change in either parameter. At 24 hours after the first dose, however, the dogs responded in much the same manner as with the first administration of phenylpropanolamine. Control dogs given water did not exhibit any degree of tachyphylaxis. Dogs anesthetized with Na pentobarbital were given oral and intravenous doses of phenylpropanolamine (0.0-25 mg/kg). The overall response was like that observed in the unanesthetized preparation with the important exception that low doses (0.1-3 mg/kg) produced significant increases in both heart rate and blood pressure, while higher doses (6-25 mg/kg) resulted in a lesser overall effect. Six anesthetized animals were used to study the effects of phenylpropanolamine and norepinephrine on the cardiovascular function. Both the increase in blood pressure and left ventricular force of contraction, produced by the first dose of phenylpropanolamine, were markedly reduced or absent with the second administration of the drug. In addition, the classic blood pressure response to norepinephrine was likewise increased by prior administration of phenylpropanolamine.(ABSTRACT TRUNCATED AT 400 WORDS)
苯丙醇胺存在于许多常用于控制食欲或作为感冒药的非处方制剂中。尽管被广泛使用,但关于其对人体心血管系统的影响仍存在一些问题。本研究使用了麻醉和未麻醉的成年比格犬。在未麻醉的条件犬中,使用可充气尾袖测量血压和心率。在第一组中,由12只犬组成,通过胃管给予苯丙醇胺(0.0、3.1、6.25和12.5毫克/千克),并对动物进行300分钟的观察。每剂苯丙醇胺给予由3只犬组成的4组。它使血压呈剂量依赖性升高,心率降低。最大变化出现在30至60分钟,持续3至5小时。第二组9只未麻醉犬反复口服苯丙醇胺(每组3只动物,共3组)。口服3毫克/千克和6毫克/千克的剂量产生的血压升高和心率降低与之前观察到的大致相同。在6小时时,相同剂量的苯丙醇胺对这两个参数几乎没有影响。然而,在首次给药后24小时,犬的反应与首次给予苯丙醇胺时大致相同。给予水的对照犬未表现出任何程度的快速耐受性。用戊巴比妥钠麻醉的犬给予口服和静脉注射苯丙醇胺(0.0 - 25毫克/千克)。总体反应与在未麻醉制剂中观察到的相似,但重要的例外是低剂量(0.1 - 3毫克/千克)使心率和血压均显著升高,而高剂量(6 - 25毫克/千克)导致的总体效应较小。使用6只麻醉动物研究苯丙醇胺和去甲肾上腺素对心血管功能的影响。首次给予苯丙醇胺所产生的血压升高和左心室收缩力增加,在第二次给药时明显降低或消失。此外,预先给予苯丙醇胺同样会增强对去甲肾上腺素的经典血压反应。(摘要截断于400字)