Taveira da Silva A M, Pineo S, Gillis R A
Department of Medicine and Pharmacology, Georgetown University Medical Center, Washington, D.C. 20007.
Pharmacology. 1992;45(1):41-51. doi: 10.1159/000138971.
The purpose of this study was to test the effects of the new beta-carboline ZK 93426 on midazolam-induced cardiorespiratory depression. Seven pentobarbital-anesthetized (35 mg/kg i.p.) cats were treated with intravenous midazolam (2 mg/kg) while monitoring the respiratory minute volume (VE), tidal volume, respiratory rate, blood pressure, heart rate and expired CO2. Midazolam caused significant decreases in VE (p less than 0.05) and blood pressure (p less than 0.05). ZK 93426 (5 mg/kg i.v.) antagonized these effects and produced significant increases in VE and blood pressure that resulted in the return of these variables to premidazolam control values. In 4 animals with morphine-induced respiratory depression, intravenous ZK 93426 failed to antagonize the respiratory effects of morphine. Administration of intravenous ZK 93426 alone to 4 pentobarbital-anesthetized animals also failed to produce significant changes in cardiorespiratory activity. We conclude that ZK 93426 is effective in counteracting the cardiorespiratory depressant effects of midazolam and that these effects appear to be specific. The present data suggest that this compound may be useful for the treatment of benzodiazepine oversedation and overdose.
本研究的目的是测试新型β-咔啉ZK 93426对咪达唑仑诱导的心肺抑制的影响。七只戊巴比妥麻醉（腹腔注射35mg/kg）的猫静脉注射咪达唑仑（2mg/kg），同时监测每分通气量（VE）、潮气量、呼吸频率、血压、心率和呼出二氧化碳。咪达唑仑导致VE（p<0.05）和血压（p<0.05）显著下降。ZK 93426（静脉注射5mg/kg）拮抗了这些作用，使VE和血压显著升高，导致这些变量恢复到咪达唑仑给药前的对照值。在4只吗啡诱导呼吸抑制的动物中，静脉注射ZK 93426未能拮抗吗啡的呼吸作用。对4只戊巴比妥麻醉的动物单独静脉注射ZK 93426也未能使心肺活动产生显著变化。我们得出结论，ZK 93426可有效对抗咪达唑仑的心肺抑制作用，且这些作用似乎具有特异性。目前的数据表明，该化合物可能对治疗苯二氮䓬类药物镇静过度和过量有用。
