In vitro interaction of diazepam and oxazepam with pancuronium and suxamethonium.
In vitro studies using the rat phrenic nerve-hemidiaphragm preparation were performed to investigate the effects of diazepam and three of its metabolites on indirectly evoked twitch tension. Diazepam, desmethyldiazepam and temazepam alone caused an increase in twitch tension in lower concentrations, followed by complete depression in higher concentrations. Oxazepam did not cause an initial increase in twitch tension, but showed an immediate and dose-dependent depression. Cumulative concentration-response curves for pancuronium and suxamethonium in the presence of different concentrations of diazepam or oxazepam showed that small concentrations of diazepam, which did not change twitch tension alone, caused antagonism of the action of pancuronium, but not of suxamethonium. With oxazepam no such antagonism was observed. In liminal and supraliminal concentrations, both diazepam and oxazepam potentiated the action of pancuronium and suxamethonium. Possible implications for in vivo interactions are discussed.
D000818:Animals; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D003708:Nordazepam / Q000494:pharmacology; D010076:Oxazepam / Q000494:pharmacology*; D010197:Pancuronium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013390:Succinylcholine / Q000494:pharmacology*; D013693:Temazepam / Q000494:pharmacology
D003708:Nordazepam; D010076:Oxazepam; D013693:Temazepam; D013390:Succinylcholine; D010197:Pancuronium; D003975:Diazepam