胆碱能M和N双靶向拮抗剂宾赛克嗪对氨基甲酸酯类克百威中毒诱发循环衰竭的救治效应  

Benthiacthiactzine,an antagonist of both muscarnic and nicotinic receptor,against circulatory failure induced by carbofuran

作　　者：王汝欢[1,2] 金鑫[3] 龙超良[3] 崔文玉[1] 汪海[3] 

机构地区：[1]北京赛德维康医药研究院,北京100039 [2]江苏恩华赛德药业有限责任公司 [3]军事医学科学院卫生学环境医学研究所心血管药物研究中心,北京100850

出　　处：《中国临床药理学与治疗学》2015年第12期1360-1366,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家新药创制科技重大专项(2009ZXJ09002-014);军队医药卫生十二五重大专项(AWS11J003)

摘　　要：目的：研究胆碱能M和N受体双靶向拮抗剂宾赛克嗪对克百威中毒诱发循环衰竭的救治效应。方法：腹腔注射克百威累积染毒致循环衰竭,肌内注射宾赛克嗪和阿托品,观察治疗前后外周血压、心功能的变化;在克百威染毒小鼠模型上研究宾赛克嗪的抗毒效应（PR值）。结果：克百威所致大鼠循环衰竭时,与染毒前相比,外周血压、心率和反映心脏收缩功能的指标均显著降低（P〈0.01）,反映心脏舒张功能的指标显著升高（P〈0.01）。与循环衰竭时相比,给予宾赛克嗪0.25-1.0 mg/kg或阿托品1.0 mg/kg治疗后,在1 min内外周血压显著升高（P〈0.05,P〈0.01）,在观察的60 min内外周血压维持平稳;在0.5-2 min内血流动力学参数各指标均脱离循环衰竭水平（P〈0.05,P〈0.01）。宾赛克嗪18 mg/kg可使小鼠抗克百威中毒的PR值提高到17.95。结论：新型抗毒剂宾赛克嗪具有速效和强效救治克百威染毒诱发循环衰竭的作用。AIM： To investigate the therapeutic effect of benthiacthiactzine,an antagonist of both muscarnic and nicotinic receptor,against circulatory failure induced by carbofuran. METHODS： Rats were treated with carbofuran（ i. p） to induce circulatory failure in which the mean blood pressure（ MBP） dropped to 40-45 mm Hg as an index,then treated with benthiactzine or atropine by i. m. The changes of peripheral blood pressure and cardiac function were observed before and after treatment.In addition,a poison resistance（ PR） value was introduced to evaluate the antidotal effect of benthiactzine and atropine in carbofuran poisoning mice.RESULTS： In circulatory failure rats induced by carbofuran,SBP,DBP,MBP,HR, ＋ dp / dtmax,Vmp,Vmaxand ＋ dp / dtmax/ IP dramatically were decreased（ P〈 0. 01） and-dp / dtmax,LVDP,IP dramatically were increased（ P 〈0. 01） compared with pre-poisoning. Benthiactzine improved each parameter in 0. 5-2 min. Administration of benthiactzine at a dose of 18 mg / m L raised the PR value of carbofuran to 17. 95. CONCLUSION： Benthiactzine has quick and potent therapeutic effects against circulatory failure induced by carbofuran poisoninge.

关 键 词：克百威 循环衰竭 宾赛克嗪 阿托品 

分 类 号：R965.2[医药卫生—药理学]