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重复给药非莫西汀的心血管(心电图和收缩期时间间期)及抗胆碱能效应——与阿米替林和安慰剂在健康男性中的比较

Cardiovascular (ECG and systolic time intervals) and anticholinergic effects of repeated doses of femoxetine--a comparison with amitriptyline and placebo in healthy men.

作者信息

Warrington S J, Turner P, Skrumsager B K

机构信息

Charterhouse Clinical Research Unit, London.

出版信息

Br J Clin Pharmacol. 1989 Mar;27(3):343-51. doi: 10.1111/j.1365-2125.1989.tb05375.x.

Abstract
  1. The cardiovascular and anticholinergic effects of femoxetine and amitriptyline were compared with those of placebo in a double-blind cross-over trial in 12 healthy men. The daily doses administered were therapeutic: 600 mg femoxetine and 150 mg amitriptyline. Duration of treatment with each drug was 13 days. 2. The statistically significant effects on systolic time intervals and ECG comprised a larger decrease of QS2 index during femoxetine than during amitriptyline, and an increase of PEP/LVET ratio and QRS duration by amitriptyline. These results suggest that femoxetine and, to a lesser extent, amitriptyline increase contractility compared with placebo, and amitriptyline, but not femoxetine, causes delay in intracardiac conduction. 3. The effects of amitriptyline on the systolic time intervals are difficult to interpret because of the changes in heart rate and intracardiac electrical conduction caused by the drug. These problems of interpretation are discussed. 4. No significant changes in blood pressure were observed. The heart rate during both femoxetine and amitriptyline periods was significantly faster than during the placebo period, amitriptyline causing a significantly greater increase. 5. Salivary secretion was decreased more by amitriptyline (26%) than by femoxetine (8%), the latter being not significantly different from placebo. Femoxetine tended to increase pupil diameter and amitriptyline to increase accommodation near point, but no visual disturbances were reported on any treatment. Symptoms such as dry mouth, constipation and sedation were significantly less frequently reported during femoxetine than during amitriptyline treatment.
摘要
  1. 在一项针对12名健康男性的双盲交叉试验中,比较了非莫西汀和阿米替林与安慰剂的心血管及抗胆碱能作用。给药的每日剂量为治疗剂量:非莫西汀600毫克,阿米替林150毫克。每种药物的治疗持续时间为13天。2. 对收缩期时间间期和心电图有统计学显著影响,包括非莫西汀治疗期间QS2指数的下降幅度大于阿米替林治疗期间,以及阿米替林使PEP/LVET比值和QRS时限增加。这些结果表明,与安慰剂相比,非莫西汀以及在较小程度上阿米替林可增加心肌收缩力,且阿米替林而非非莫西汀会导致心内传导延迟。3. 由于该药物引起的心率和心内电传导变化,阿米替林对收缩期时间间期的影响难以解释。讨论了解释方面的这些问题。4. 未观察到血压有显著变化。非莫西汀和阿米替林治疗期间的心率均显著快于安慰剂治疗期间,阿米替林引起的心率增加更为显著。5. 阿米替林使唾液分泌减少26%,多于非莫西汀的8%,后者与安慰剂无显著差异。非莫西汀倾向于增加瞳孔直径,阿米替林倾向于增加近点调节,但在任何治疗中均未报告视觉障碍。与阿米替林治疗相比,非莫西汀治疗期间口干、便秘和镇静等症状的报告频率显著更低。

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