Gamma-aminobutyric acid type A receptor blockade at the intermediate area of the ventral surface of the medulla counteracts the cardiorespiratory depression produced by intravenous midazolam.
Intravenous administration of midazolam (2 mg/kg) to 8 pentobarbital-anesthetized cats produced a significant decrease in minute ventilation, tidal volume, blood pressure and heart rate. Treatment with the gamma-aminobutyric acid (GABA) type A receptor antagonist bicuculline (10 micrograms/side) at the intermediate area of the ventral surface of the medulla (VSM) oblongata completely reversed the cardiorespiratory depressant effects of intravenous midazolam. In contrast, treatment with bicuculline at the same area failed to counteract the respiratory depressant effects of intravenous morphine (1 mg/kg). We conclude that the cardiorespiratory depressant effects of intravenously administered midazolam are due to enhancement of GABAergic transmission at the intermediate area of the VSM.
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; D001640:Bicuculline / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects*; D002415:Cats; D058787:GABA-A Receptor Antagonists; D008526:Medulla Oblongata / Q000187:drug effects*; D008874:Midazolam / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D009020:Morphine / Q000037:antagonists & inhibitors; D009270:Naloxone / Q000494:pharmacology; D010424:Pentobarbital; D012137:Respiratory System / Q000187:drug effects*
D058787:GABA-A Receptor Antagonists; D009270:Naloxone; D009020:Morphine; D010424:Pentobarbital; D008874:Midazolam; D001640:Bicuculline