Analgesic Mechanism and Research Progress on Improved Preparations and New Dosage Forms of Lappaconitine

Abstract

Lappaconitine is a non-addictive central analgesic independently developed in China with prominent analgesic activity. However, its further clinical application is restricted by poor water solubility, insufficient stability, narrow therapeutic window, and potential cardiotoxicity. In recent years, research on lappaconitine has gradually shifted from pharmacodynamic observations to mechanistic investigations, structural optimization, and novel formulation development. This review summarizes the analgesic mechanisms, pharmacokinetic characteristics, clinical limitations, as well as advances in modified drugs and novel dosage forms of lappaconitine. Current evidence indicates that lappaconitine exerts analgesic effects through multiple pathways, including regulating neurotransmitters, interfering with pain signal transmission in the spinal cord and dorsal root ganglia, inhibiting peripheral ion channel activity, and suppressing neuroinflammation. To overcome its suboptimal druggability, structural modification and formulation optimization have shown considerable potential in improving efficacy, safety, and pharmacokinetic profiles. Overall, lappaconitine remains a promising candidate for further research and development, but its detailed analgesic mechanisms, structure–activity relationships, and clinical translation still require in-depth exploration.