A beta-carboline derivative (ZK 93426) counteracts the cardiorespiratory depressant effects of intravenous midazolam.
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.
Taveira da Silva
A M
AM
Department of Medicine and Pharmacology, Georgetown University Medical Center, Washington, D.C. 20007.
Pineo
S
S
Gillis
R A
RA
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D002415:Cats; D003864:Depression, Chemical; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D008874:Midazolam / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects*
D000927:Anticonvulsants; D002243:Carbolines; D009020:Morphine; C042568:ZK 93426; D008874:Midazolam; D004121:Dimethyl Sulfoxide