羟基哌喹的急性毒性  

ACUTE TOXICITY OF HYDROXYPIPERAQUINE

作　　者：沈念慈[1] 唐惠兰 李保春[1] 姜渭 周志秋 郑昌万 吕浩[3] 刘巧年 

机构地区：[1]第二军医大学抗疟药研究室 [2]第二军医大学训练部药理学教研室 [3]第二军医大学放射医学研究室

出　　处：《第二军医大学学报》1989年第4期318-322,共5页Academic Journal of Second Military Medical University

摘　　要：本文报道磷酸羟基哌喹(hydraxypipoxaquino tetraphosphate,HPQP)对小鼠、家兔和犬的急性毒性,并与磷酸氯喹(chloroquine diphospate,CQP)对比。HPQPi.g.对小鼠的LD_(50)为439.0～e83.1mg/kg;CQPi.g.的LD_(50)为266.1～377.5mg/kg。HpQPi.V.对犬的惊厥量和致死量均为40πg/kg;i.g.对犬的惊厥量和致死量分别为200和600mg/kg,均显著高于CQP。两药的中毒表现均为胆碱能神经和中枢神经的兴奋体征,i.v.和CQP的中毒表现分别比i.g.和HPQP出现早而严重,所不同者CQP均不致吐。HPQP所致肝脏组织病理变化属可逆性。HPQP对家兔的心血管毒性显著低于CQP,且不产生室颤。急性毒性试验的结论为:HPQP的急性毒性小于CQP,安全范围大于CQP,有较好的前景。Hydroxypiperaquine (HPQ) and its phosphate (HPQP) are a new long-acting antimalarial agent synthesized in our Lab.The 95% fiducial limits of i.g.LD50 of HPQP and chloroquine phosphate (CQP) in mice were 387~491 and 253~330 mg/kg, respectively.The i.v.convulsive doses of HPQP and CQP in dogs were 40 and 8 mg/kg, respectively.The i.g.convulsive doses of HPQP and CQP in dogs were 200 and 40 mg/kg, while their MLD were 600 and 40 mg/kg, respectively.The acute cardiovascular toxicity of HPQP in rabbits was lower than that of CQP significantly.The intoxicated manifestations of HPQP in dogs were characterized by the signs of stimulation of cholinergic and central nervous system such as emesis, excitation, salivation, urination, defecation, tremor and convulsion.The acute toxic manifestations of CQP were similar to those of HPQP but developed more rapidly and markedly.The transient elevated activities of sGPT demonstrated that hepatic function was impaired to some extent and that th; liver may be the toxic target organ.The results obtained show that HPQP has a lower toxicity and a broader margin of safety as compared with CQP.Thess results may be useful for the control of its side effects during clinical use.

关 键 词：羟基哌喹 抗疟药 毒理学 

分 类 号：R978.61[医药卫生—药品]