Comparative acute toxicity of quaternary ammonium lidocaine derivative QX-314 to lidocaine in mice

Lee, Sang Mook; Chung, Kyu Don; Son, Yoon Suk; Yu, Sung Jun; Ryu, Keon Hee; Lee, Sang Hoon; Cho, Hyun Sook

Abstract

BACKGROUND: The current study examined the acute systemic toxicity of QX-314 that there have been few research results for this so far. In order to be useful as a drug, it must be shown to have minimal toxicities. Hence, we compared the CNS and cardiac toxicities of QX-314 to the conventional local anesthetic lidocaine.
METHODS
Acute toxicity was evaluated by determining the individual intravenous CD50 and LD50 of QX-314 and lidocaine. There were four doses for each LD50 determination and 8 animals per dose level. Animals were observed for several hours immediately following drug administration and recorded overt effects and fatalities. Both lidocaine and QX-314 were dissolved in saline. Lidocaine and QX-314 were diluted to 1, 2, 4, 6 and 0.5, 1, 2, 4%, respectively with saline and injected at the same volume to minimized cardiovascular effect.
RESULTS
The intravenous CD50 and LD50 were 12.7 and 14.1 mg/kg for QX-314 and 15.7 and 28.8 mg/kg for lidocaine. Electrocardiograms showed intraventricular block (widened QRS complex) at high doses of lidocaine compared to AV block (loss of QRS complex) at high concentrations of QX-314. There are no evidence that CNS toxicity led mouse to death.
CONCLUSIONS
QX-314 is about 1.5 times as toxic as lidocaine. Although QX-314 may still be useful clinically as a long-lasting local anesthetic, its safety relative to other available local anesthetics must be considered.