Interaction of some benzodiazepines and their solvents with vecuronium in the in vivo rat sciatic nerve-tibialis anterior muscle preparation.
Interaction studies between different injectable benzodiazepines and vecuronium, a non-depolarizing neuromuscular blocking drug, were performed in the rat in vivo sciatic nerve-tibialis anterior muscle preparation. The investigated doses were aimed to be "sedative" in the rat. A significant antagonism of a steady state depression of the twitch height induced by vecuronium was observed during approximately 10 min after i.v. injection of those benzodiazepines containing organic solvents in their formulations (diazepam, desmethyldiazepam, oxazepam, temazepam, lorazepam and lormetazepam). This antagonism is mainly due to propylene glycol, the main organic solvent for the poorly water-soluble benzodiazepines. After the initial antagonism, a potentiation of the vecuronium-induced depression occurred with some of these benzodiazepines (diazepam, desmethyldiazepam, temazepam and lormetazepam). Two water-soluble benzodiazepines, midazolam and flurazepam, caused a significant potentiation of the vecuronium-induced block. Important side-effects (blood pressure drop, convulsions, hematuria) were observed with the amount of propylene glycol present in the investigated formulation of lormetazepam.
Driessen
J J
JJ
Vree
T B
TB
van Egmond
J
J
Booij
L H
LH
Crul
J F
JF
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D009119:Muscle Contraction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D010197:Pancuronium / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000187:drug effects; D012995:Solubility; D012997:Solvents / Q000494:pharmacology*; D014673:Vecuronium Bromide
D012997:Solvents; D001569:Benzodiazepines; D014673:Vecuronium Bromide; D010197:Pancuronium