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口服司来吉兰和雷沙吉兰对清醒家兔QT间期影响的研究。

Investigation of oral selegiline and rasagiline administration on QT interval in conscious rabbits.

作者信息

Uzun M, Alp R, Uzlu E, Alp S, Citil M, Topcu B, Erdogan H M

机构信息

School of Health Science, Canakkale Onsekiz Mart University, Canakkale, Turkey.

出版信息

Eur Rev Med Pharmacol Sci. 2009 Mar-Apr;13(2):95-8.

Abstract

Rasagiline (RSG) and selegiline (SEL) are potent selective monoamine oxidase-B inhibitors and used in the treatment of Parkinson's disease. Selegiline is metabolized in vivo to I-methamphetamine and I-amphetamine which effect cardiovascular system. Therefore, the aim of this study was to evaluate and to compare the effects of long-term use of these drugs on QT interval in conscious rabbits. The study involved 17 New Zealand rabbits of both sexes, aged between 7 and 14 months. Control group (CG, n = 6) was orally given isotonic saline solution at dose of 0.5 cc/per rabbit. The SEL group (SG, n = 6) received 5 mg/per rabbit SEL orally twice daily (09:00 am and 09:00 pm) for 14 days. The RSG group (RG, n = 5) was orally given of RSG at 1 mg/per rabbit daily for 14 days. Electrocardiographic records were taken before the experiment (baseline) and at 1st, 7th, and 14th days of experiment by direct writing electrocardiograph for two groups. Heart rate (HR), QT and QTc values were determined from ECG records. HR did not significantly differ in both treatment groups through the experimental period when compared to baseline values. The significant prolongation of QT and QTc values were observed at 7th, and 14th day (p < 0.01) in SG and 1st day of experiment in RG (p < 0.05) as compared to baseline values. In conclusion, the results obtained suggest a statistically significant effect of SEL on QTc prolongation when compared to RAS. QTc prolongations should be taken into account in Parkinson's disease where autonomic system is involved.

摘要

雷沙吉兰(RSG)和司来吉兰(SEL)是强效的选择性单胺氧化酶-B抑制剂,用于治疗帕金森病。司来吉兰在体内代谢为1-甲基苯丙胺和1-苯丙胺,它们会影响心血管系统。因此,本研究的目的是评估和比较长期使用这些药物对清醒家兔QT间期的影响。该研究涉及17只7至14个月大的新西兰雌雄家兔。对照组(CG,n = 6)每只家兔口服0.5 cc的等渗盐溶液。司来吉兰组(SG,n = 6)每只家兔每天口服5 mg司来吉兰,分两次给药(上午9:00和晚上9:00),持续14天。雷沙吉兰组(RG,n = 5)每只家兔每天口服1 mg雷沙吉兰,持续14天。通过直接记录心电图仪在实验前(基线)以及实验的第1、7和14天对两组进行心电图记录。从心电图记录中确定心率(HR)、QT和QTc值。与基线值相比,在整个实验期间,两个治疗组的HR均无显著差异。与基线值相比,SG组在第7天和第14天观察到QT和QTc值显著延长(p < 0.01),RG组在实验第1天观察到QT和QTc值显著延长(p < 0.05)。总之,与雷沙吉兰相比,所得结果表明司来吉兰对QTc延长具有统计学显著影响。在涉及自主神经系统的帕金森病中应考虑QTc延长。

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