Lumbar intrathecal administration of the quaternary lidocaine derivative, QX-314, produces irritation and death in mice.
BACKGROUND
We recently found that peripheral administration of the quaternary lidocaine derivative, QX-314, produces long-lasting sensory and motor blockade in animals. The goal of this study was to test whether intrathecal QX-314 has similar properties.


METHODS
We conducted a randomized, double-controlled, blinded study with female CD-1 mice. Animals in the treatment group received lumbar intrathecal QX-314 (0.5-10 mM; volume, 2 microl; each concentration, n = 6). Normal saline and lidocaine (70 mM) served as negative and positive controls (each group, n = 12), respectively. Animals were tested for up to 3 h for lumbosacral neural blockade and observed for adverse effects.


RESULTS
No animal injected with saline and 11 of 12 (92%) animals injected with lidocaine displayed reversible lumbosacral motor blockade (P < 0.001). QX-314 (5 mM) produced motor blockade in four of the six (67%) and sensory blockade in five of the six animals (83%; P < 0.05 vs. saline). However, six of the six mice (100%) at 5 mM QX-314 and five of the six (83%) at 10 mM exhibited marked irritation; one of the six animals at 5 mM (17%) and two of the six at 10 mM (33%) died. We observed no neural blockade without adverse effects in any animal injected with QX-314. All animals injected with saline and 11 of the 12 (92%) animals injected with lidocaine demonstrated normal behavior.


CONCLUSIONS
Lumbar intrathecal QX-314 concentration-dependently produced irritation and death in mice, at lower concentrations than those associated with robust motor blockade. Although QX-314 did produce long-lasting neural blockade, these findings indicate that QX-314 is unlikely to be a suitable candidate for spinal anesthesia in humans.
Schwarz
Stephan K W
SK
St. Paul's Hospital, Vancouver, British Columbia, Canada. stephan.schwarz@ubc.ca
Cheung
Helen M-C
HM
Ries
Craig R
CR
Lee
Sang Mook
SM
Wang
Jimmy T C
JT
MacLeod
Bernard A
BA
D017109:Akathisia, Drug-Induced / Q000175:diagnosis / Q000401:mortality*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D007278:Injections, Spinal; D008012:Lidocaine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000633:toxicity; D008161:Lumbosacral Region; D051379:Mice; D011537:Pruritus / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality*; D011897:Random Allocation
C012647:QX-314; D008012:Lidocaine