title: Effect of midazolam pretreatment on the intravenous toxicity of lidocaine with and without epinephrine in rats.
abstract: The effect of the benzodiazepine midazolam on the intravenous toxicity of lidocaine with and without epinephrine was studied in male Sprague-Dawley rats. Test rats with and control rats without midazolam premedication (2.5 mg/kg intraperitoneally, 10% of the median dose that caused loss of the righting reflex in a third group of rats) were given 2% lidocaine with and without 10 micrograms/ml epinephrine intravenously in doses sufficient to construct log-dose response curves for both convulsant and lethal responses. In control rats the median convulsant dose (CD50) of lidocaine was 15.2 mg/kg given alone and 10.9 mg/kg with epinephrine (a statistically significant difference); respective values for the median lethal dose (LD50) were 26.4 and 18.5 mg/kg (also statistically significant). While epinephrine enhanced lidocaine seizure activity and lethality by approximately 50%, midazolam almost completely prevented lidocaine-induced convulsions but had no significant effect on mortality.
authors.affiliation: Section of Oral Biology, UCLA School of Dentistry 90024.
authors.forename: M L
authors.initials: ML
authors.lastname: Torbiner
authors.forename: J A
authors.initials: JA
authors.lastname: Yagiela
authors.forename: R S
authors.initials: RS
authors.lastname: Mito
mesh_terms: D000818:Animals; D004347:Drug Interactions; D004837:Epinephrine / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008012:Lidocaine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D011229:Preanesthetic Medication; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D008012:Lidocaine; D008874:Midazolam; D004837:Epinephrine