HR0905安全药理学研究

Study on safety pharmacology of HR0905

目的观察HR0905对小鼠神经系统、犬心血管系统及呼吸系统的影响。方法实验均分HR0905高、中、低剂量组及溶媒对照共4个组,小鼠实验给药组分别单次灌胃(ig)HR0905 30,100和300 mg/kg,观察药物对小鼠自发活动和爬杆能力的影响;犬实验给药组分别单次igHR0905 2、6、20 mg/kg,观察药物对犬血压、ECG、呼吸频率及节律的影响。结果与溶媒对照组相比,HR0905单次ig后高剂量组爬杆能力显著下降;给药后1.5 h开始动物自发活动有下降趋势,且3.5 h下降最多;HR0905单次ig后犬心率明显减慢。给药后2.0 h中剂量组及高剂量组Beagle犬收缩压、舒张压及平均动脉压有下降趋势,且4.0 h下降幅度最大。HR0905对Beagle犬ECG之P波电压、T波电压、QRS时间、PR间期、QT间期、ST段无明显影响;HR0905对呼吸频率、幅度和节律无明显影响。结论 HR0905对心血管和神经系统有一定的影响,可使犬心率减慢,犬收缩压、舒张压及平均动脉压有下降趋势,小鼠爬杆能力显著下降,自发活动有下降趋势。

Objective To study the effects of HR0905 on nervous system of mice and cardiovascular and respiratory systems of beagle dogs.Methods The mice were randomly divided into high,medium and low dose group and control group which received a single dose of 30,100,300 and 0 mg/kg of HR0905 by intragastric（ig） administration respectively and the spontaneous activities and pull-down ability of animals were observed.The beagle dogs were also randomly divided into high,medium and low dose group and control groups which received a single dose of 2,6,20 and 0 mg/kg HR0905 by ig administration respectively and the blood pressure,ECG,respiratory rate and width of dogs were measured.Results Compared with the vehicle control group,the pole climbing ability of the high dose group decreased significantly after a single ig administration of HR0905.Then a downward trend of spontaneous activity was observed in the animals 1.5 h after the administration,and the peak value was detected at 3.5 h.After a single ig administration of HR 0905,the heart rate of beagle dogs decreased significantly.The systolic blood pressure,diastolic blood pressure,mean arterial pressure,heart rate and respiratory rate of beagle dogs were decreased 2.0 h after administration in the medium and high dose groups,and the peak vale was detected at 4.0 h after administration.HR0905 had no significant effects on P-wave voltage,T wave voltage,QRS interval,PR interval,QT interval,ST segment of ECG of Beagle dogs.HR0905 had no significant effects on respiratory frequency,amplitude and rhythm in Beagle dogs.Conclusion HR0905 had certain effects on cardiovascular and nervous system.The compound could decrease the heart rate of the dogs.There was a downward trend in systolic blood pressure,diastolic blood pressure,mean arterial pressure of beagle dogs.The pole climbing ability of mice decreases significantly and spontaneous activity experiences a downward trend.