Analgesic effects and sensory neuron selectivity of amiodarone

2022 Fiscal Year Final Research Report

• Project/Area Number: 19KK0417
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: University of Yamanashi
• Principal Investigator: Kotoda Masakazu 山梨大学, 大学院総合研究部, 講師 (30530133)
• Project Period (FY): 2020 – 2022
• Keywords: アミオダロン

Outline of Final Research Achievements

Anesthetic profiles and effects on the sensory neurons and other cells were evaluated using various murine models. Perineural administration of amiodarone showed longer anesthetic effect, compared with commonly-used local anesthetics. Coadministration with capsaicin selectively prolonged the anesthetic effects on sensory neurons, indicating that capsaicin facilitated TRPV1 channel-mediated entry of amiodarone into the neurons. Amiodarone showed analgesic effects at even lower doses in inflammatory pain models. Amiodarone derivatives were also tested for the analgesic and antiarrhythmic profiles. Among the drugs tested, dideiodoamiodarone showed potent and long-lasting anesthetic effects as well as local toxicity. Dideiodoamiodarone showed amiodarone-like antiarrhythmic profiles. However, the LD50 was significantly lower than that of amiodarone.

Free Research Field

疼痛

Academic Significance and Societal Importance of the Research Achievements

麻薬性鎮痛薬を始めとして現在数多くの鎮痛薬が臨床の場で使用されているが、呼吸抑制や依存性など依然として課題が多い。副作用の少ない新規鎮痛薬の発見・開発が切望されている。本研究成果は、アミオダロンおよびその類縁化合物が潜在的に麻酔作用・鎮痛作用を有すことを示唆しており、カプサイシンなどのTRPチャネル開口薬との併用や、炎症性疼痛などターゲットとなる病態を絞った使用法により、既存の鎮痛薬や麻酔薬と比較し、強力で長時間の作用が得られる可能性を示している。