目的:观察盐酸椒苯酮胺(PPTA)对大鼠和Beagle犬的急性毒性反应,计算最大给药量并评价其安全性.方法:对SD大鼠分别ig和iv给药,单次剂量为50 mg/kg,间隔4~6 h,连续3次,总剂量为150 mg/kg,给药后连续14 d观察PPTA给药组(n=40)和溶剂对照组(n=20)大鼠毒性反应及体质量等.对Beagle犬单次ivgtt PPTA最大给药剂量200 mg/kg,给药后连续14 d观察PP-TA给药组(n=4)和溶剂对照组(n=3)Beagle犬的一般生理指标、体质量、体温、心电指标、血压、血浆电解质、尿液、眼科和病理学指标等.结果:大鼠经ig给药后未见明显异常表现,但iv给药数分钟内出现一过性的行动不稳,连续观察14 d均未见异常情况;给药组大鼠体质量均增长正常.Beagle犬给药过程出现一过性结膜充血、恶心呕吐、流涎、眼睑轻微水肿和后肢无力,有1只出现膀胱出血致尿血的现象;给药后14 d内给药组犬体质量与体温变化情况与溶剂对照组比较,差异无统计学意义(P>0.05),其他各项指标均未观察毒性反应相关的异常改变.结论:大鼠ig和iv给予PPTA的半数致死量(LD50)值均大于150 mg/kg;Beagle犬单次ivgtt给予PPTA 200 mg/kg未导致犬死亡,给药后所出现的异常体征为该药的毒副反应,膀胱出血等可能是该药主要的毒性反应.“,”OBJECTIVE:To investigate acute toxicity of piperphentonamine hydrochloride (PPTA) in rats and Beagle dogs, and to calculate maximum dosage and evaluate its safety. METHODS:SD rats were given relevant medicine via ig or iv,at a sin-gle dose of 50 mg/kg,every 4-6 h,for consecutive 3 times,150 mg/kg in total;after 14 d treatment,the toxicity reaction and body weight of rats were observed in PPTA group (n=40) and solvent control group (n=20). Beagle dogs were given PPTA ivgtt,at maximal single dose of 200 mg/kg;after 14 d of treatment,Beagle dogs of PPTA group(n=4)and solvent control group (n=3) were observed in respects of general physiological index,body weight,body temperature,ECG index,blood pressure, plasma electrolyte,urine,ophthalmology and pathological index,etc. RESULTS:There was no obvious abnormality in rats after ig administration of PPTA. One-off action instability occurred after iv within minutes;no abnormality was found for 14 days;the increase of body weight of rats in treatment groups was normal. Transient conjunctival congestion,nausea and vomiting,saliva-tion,mild edema eyelids and rear limb weakness were observed in Beagle dogs during dosing;only one Beagle dog suffered from hematuria caused by hemorrhage of bladder. 14 d after medication,there was no statistical significance in body weight and tempera-ture of Beagle dogs between treatment groups and solvent control group(P>0.05). No abnormal changes due to drug toxicity reac-tion were observed. CONCLUSIONS:LD50 values of PPTA in rats via ig and iv are over 150 mg/kg. Beagle dogs did not died at the single dose of 200 mg/kg PPTA,ivgtt. The abnormal signs of animals may be the side effects of PPTA. The main toxic reaction of PPTA may be hemorrhage of bladder and other.