安吖啶的一般药理和组织刺激性研究

GENERAL PHARMACOLOGICAL STUDY AND LOCAL TISSUE IRRITATION OF AMSACRINE

用电子活动仪测定给药前后小鼠的活动情况.结果证明,静脉注射2.5或10mg/kg安吖啶后小鼠活动正常,无不良反应.在5只麻醉兔中用多导生理记录仪连续观察了给予3种不同剂量安吖啶后对血压、呼吸及心电图的影响.结果表明,给小鼠静脉注射最大有效剂量4.4mg/kg,对血压、呼吸无影响,心电图也未发现异常.静脉注射10mg/kg后,2/5兔中有一过性血压下降,伴有心电图一过性Ⅱ°房室传导阻滞.给予30mg/kg(急性致死剂量),3/3兔中均引起血压下降,除Ⅱ°房室传导阻滞外,还出现室性期外收缩.在6只家兔中采用台盼蓝试验,观察了药物对组织的刺激作用.结果表明,未经5%葡萄糖稀释的高浓度组(0.5%,0.2%),注射后4～24h.对皮肤、肌肉及血管有较强刺激性,而其他低浓度组(0.1%,0.03%,0.015%)对皮肤及血管无任何刺激.

The spontaneous activity of mice after iv injection of amsacrine was monitored by the electronic activity recorder.At 2.5 and 10mg/kg doses the activity of mice was similar to the control animals,no CNS toxic effect was present.The effects of amsacrine on blood pressure,ECG and respiration at three different dose levels were investigated in anesthetized rabbits by an electronic polygraph.No cardiovascular toxic effect could be found after iv injection of 4.4mg/kg amsacrine in all five rabbits studied.At 10mg/kg a temporary hypotensive effect could be seen in two of five rabbits,accompanied with A-V block of grade 2 in the ECG.Increasing the dose to 30mg/kg (acute lethal dose) significant hypotension occurred in all of the three rabbits studied,accompanied with A-V block and ventricular extrasystoles.No respiratory toxic effect could be found in all rabbits tested.The tissue irritation of amsacrine was examined by trypan blue test.At undiluted high concentrations(0.5%,0.2%)significant tissue irritation effect could be seen 4-24 h after injection.At the clinically used concentrations (0.1%,0.03% and 0.015%) no tissue irritation could be found.