Open Collections

Abstract

Current limitations of local anesthetic agents for postoperative analgesia such as lidocaine and bupivacaine include limited duration of action, undesired motor blockade, and high systemic toxicity. Recent interest in quaternary derivatives of conventional aminoamide local anesthetics arises from their reported long duration of action as well as potential for separation of sensory and motor effects, fuelling aspirations that a more ideal agent for clinical use be identified. The viability of these agents in clinical use is currently limited by toxicity and a gap in knowledge of their comparative pharmacodynamic profiles. This study aimed to address the knowledge gap by elucidating the relative potencies and efficacies of three quaternary lidocaine derivatives (QX314, QX-222, QX-572) in producing sensory blockade in mice. Two established in vivo behavioral assays, the hypertonic saline assay and the hot plate analgesic assay, were used to establish concentration-response relationships over a period of 4 hours for each drug. The experiments found that QX-572 outperformed QX-314, which outperformed QX-222 in terms of efficacy in both assays. With regards to overall relative potency, QX-572 was more potent than both QX-314 and QX-222. QX-314 and QX-222 were more potent at ameliorating nociceptive behavior elicited from the hypertonic saline assay compared to that elicited from the hot plate assay. These experiments reaffirm that quaternary lidocaine derivatives have longer durations of action than conventional aminoamide local anesthetics. Additionally, the results of these experiments have provided a basis for some speculation on the structure-affinity relationships between quaternary lidocaine derivatives. Further research is required to explore these questions and may bring us a step closer to finding local anesthetics with more desirable properties that is devoid of current clinical limitations.