复方马钱子碱的镇痛作用及其药效动力学初步观察

Analgesia and Pharmacodynamics of Compound Brucine Injection in Mice

目的探讨复方马钱子碱的镇痛作用及其药效动力学规律。方法①小鼠腹腔注射不同剂量的复方马钱子碱,于药前和药后测定痛阈(热板法),计算痛阈增加率,以各组最大药效进行量效关系计算,并与吗啡进行平行比较。②小鼠腹腔注射32.6mg/kg复方马钱子碱,药前和药后不同时间测定小鼠痛阈,绘制时间-效应曲线。根据时效曲线进行房室拟合并计算药效动力学参数。结果复方马钱子碱3个剂量均有明显的镇痛作用,其中32.6mg/kg的镇痛作用超过吗啡,差异有显著性意义。复方马钱子碱腹腔注射吸收速率常数(Ka)=0.09477/min,吸收相半衰期(T1/2a)=7.3min,消除速率常数(Ke)=0.00203/min,消除相半衰期(T1/2e)=341.4min,起效时间(Tb)=1.3min,达峰时间(Tmax)=41.4min,峰强度(Emax)=238.5,失效时间(Te)=598.7min,药效持续时间(Tc)=597.4min。结论复方马钱子碱腹腔注射有明显的镇痛作用,且起效迅速,作用强而持久。

Objective To study the anageslc enect of compounu brucine and its pharmacodynamics. Methods The mice were treated ip only once with compound brucine （32.6, 22.8, 16 mg/kg） and morphine （10 mg/kg） as positive control. Then the change of the latencies of licking paws on hot-plate were observed. The dose-effect and time-effect curves were studied. The apparent parameters of pharmacodynamics were estimated based on time-effect curves of compound brucine 32.6 mg/kg ip. Results Compound brucine can prolong the incubation period of pain caused by hot-plate in mice obviously. A significant dose- effect relationship was noted in the anagesic experenment. The potency of this drug （22.8, 16 mg/kg） ip was equivalent to that of the morphine 10 mg/kg ip. The time-effect curve after compound brucine 32.6 mg/kg ip was found to fit a 1-compartment open model with first order elimination. The apparent pharmacodynamic parameters were： Ka=0.09477/min, T1/2a=7.3 min, Ke=0.00203/min, T1/2e=341.4 min, Tb=1.3 min, Tmax=41.4 min, Emax=238.5, Te=598.7 min, Tc=597.4 min, respectively. Conclusion Compound brucine has remarkable analgesic effect with power potency and long duration.