既存嫌酒薬 ジスルフィラムによる向精神薬開発

• Published in: 日本薬理学会年会要旨集 p. 3-B-P-100
• Main Authors: 松浦, 航太, 木下, 博之, 永井, 康正, 安部, 寛子, 太田, 有紗, 松島, 綱治, 山田, 大輔, 林, 侑, 斎藤, 顕宜, 寺島, 裕也, 藤塚, 亮次
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2023
• Subjects: anxiolytic; depression
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.97.0_3-B-P-100

Aldehyde dehydrogenase inhibitor disulfiram (DSF) is used as a treatment for alcoholism. Recently, we have reported that DSF inhibits FROUNT, a molecule that promotes inflammatory chemokine receptor CCR2/5 signaling and exhibits anxiolytic-like effects in addition to anticancer effects. However, DSF shows several side effects due to the accumulation of acetaldehyde induced by inhibition of aldehyde dehydrogenase in the liver. These unwanted effects limit the development of psychotropic drugs by DSF. On the other hand, intranasal administration has been shown to selectively deliver drugs from the nose to the brain and reduce peripheral side effects. Therefore, we focused on intranasal administration, which has the potential to reduce peripheral side effects and to deliver drugs to the brain selectively.The anxiolytic-like effects of DSF were investigated using an elevated plus-maze (EPM) test. Oral and intranasal administration of DSF increased the amount of time spent in the open arms of the maze. However, ethanol administration after oral administration of DSF showed the significant decrease in body temperature and increase in blood acetaldehyde concentration 2 hours later. On the other hand, rats treated with intranasal DSF did not show the side effects 2 hours after ethanol administration. We propose that intranasal preparation of DSF is expected to be a novel psychotropic drug with a different mechanism of action combined efficacy and safety.