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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 &mgr;l; 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. Conclusion: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.