ACUTE TOXICITY OF HYDROXYPIPERAQUINE / 第二军医大学学报

ABSTRACT

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.