Newswise — In the search for a long-lasting, non-opioid, postoperative local anesthetic that would reduce the need for opioid-based pain control, various lidocaine derivatives have been suggested. In a new study, researchers from the University of British Columbia in Vancouver, Canada, tested three experimental quaternary lidocaine derivatives—QX-314, QX-572, and QX-222—in mice to compare efficacy and toxicity rates.
Desmond Fung, Helia Shariati, Michael Smith, Bernard MacLeod, Ernest Puil, and Stephan Schwarz received a Best of Meeting Abstract and Resident/Fellow Travel Award for their abstract of the study, “Motor Block Produced by Quaternary Lidocaine Derivatives: A Preclinical Comparison of QX-572 and QX-222 Versus QX-314 in Mice,” which was accepted for the 45th Annual Regional Anesthesia and Acute Pain Medicine Meeting. The meeting was scheduled for April 23-25 but was cancelled due to COVID-19.
Fung et al. conducted a randomized, double-controlled, blinded in vivo study using the sciatic nerve blockade assay in mice. They injected QX-314, QX-572, and QX-222, with lidocaine as the positive control and saline as the negative control, into the mice’s popliteal fossa on the left hindlimb. They monitored the animals for recovery from motor blockade and behavioral signs of systemic toxicity.
All three derivatives produced motor blockade at certain concentrations. QX-314 (at ≥ 3 mM) offered reversible motor blockade that lasted longer than that of lidocaine. QX-572 produced longer-lasting motor blockade than lidocaine; however, the nerve block became irreversible at > 30 mM. QX-222 resulted in reversible motor blockade similar to lidocaine at an equimolar concentration. When given at an equimolar 70 mM concentration, the median motor block durations were 0.5 hours for lidocaine, 44 hours for QX-314, and 10 minutes for QX-222. In comparison, at just 30 mM, the median block duration was 24 hours for QX-572.
“The order of potency was QX-572 > QX-314 > QX-222, which is similar to the findings from our companion study on sensory blockade,” Fung et al. said. “QX-222 may confer more favorable toxicity and sensory-motor nerve separation profiles compared to QX-314, as it did not produce long-lasting motor blockade like QX-314.
“Overall, these results indicate that hydrophobic properties influence the potency and duration of motor blockade produced by quaternary compounds,” they concluded. “Future studies with other quaternary compounds may reveal specific structural modifications that produce greater sensory-motor fiber separation with respect to local anesthetic-blocking profiles.”
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