The Quaternary Lidocaine Derivative QX-314 Produces Long-Lasting Intravenous Regional Anesthesia in Rats

BACKGROUND: The lidocaine derivative, QX-314, produces long-lasting regional anesthesia in various animal models. We designed this study to examine whether QX-314 could produce long-lasting intravenous regional anesthesia (IVRA) in a rat model. METHODS: IVRA was performed on tail of rats. EC(50) (median effective concentration) of QX-314 in IVRA was determined by up-and-down method. IVRA on tail of rats was evaluated by tail-flick and tail-clamping tests. For comparison between QX-314 and lidocaine, 60 Sprague-Dawley rats were randomly divided into 6 groups (n = 10/group), respectively receiving 0.5 ml of 0.5% lidocaine, 0.25% QX-314, 0.5% QX-314, 1.0% QX-314, 2.0% QX-314 and normal saline. To explore the role of TRPV1 channel in IVRA of QX-314, 20 rats were randomly divided into 2 groups (n = 10/group), respectively receiving 0.5 ml of 1% QX-314 and 1% QX-314+75 µg/ml capsazepine. Toxicities of QX-314 on central nervous system and cardiac system were measured in rats according to Racine's convulsive scale and by electrocardiogram, respectively. RESULTS: QX-314 could produce long-lasting IVRA in a concentration-dependent manner. EC(50) of QX-314 in rat tail IVRA was 0.15±0.02%. At concentration of 0.5%, IVRA duration of QX-314 (2.5±0.7 hour) was significantly longer than that of 0.5% lidocaine (0.3±0.2 hour, P<0.001). TRPV1 channel antagonist (capsazepine) could significantly reduce the effect of QX-314. For evaluation of toxicities, QX-314 at doses of 5 or 10 mg/kg did not induce any serious complications. However, QX-314 at dose of 20 mg/kg (1% QX-314 0.5 ml for a rat weighing 250 g) induced death in 6/10 rats. CONCLUSIONS: QX-314 could produce long-lasting IVRA in a concentration-dependent manner. This long-lasting IVRA was mediated by activation of TRPV1 channels. Evaluation of toxic complications of QX-314 confirmed that low but relevant doses of QX-314 did not result in any measurable toxicity.