Effect of perampanel on acute and chronic itch in mice

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16294
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46030:Function of nervous system-related
• Research Institution: University of Miyazaki
• Principal Investigator: Haruta-Tsukamoto Ayaka 宮崎大学, 医学部, 助教 (80773316)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 痒み / AMPA受容体 / ペランパネル / 引っ掻き行動 / マウス

Outline of Final Research Achievements

It is well known that it exerts its effects by binding to various glutamate receptors including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and that AMPA/kainate receptors play a crucial role in pruriceptive processing; however, the precise role of AMPA receptors remains uncertain. Perampanel, an antiepileptic drug, is an antagonist of AMPA receptors. Pretreatment with perampanel dose-dependently attenuated the induction of scratching, a behavior typically associated with pruritus, by intradermal administration of the pruritogen chloroquine. In addition, the induction of scratching in mice painted with diphenylcyclopropenone and NC/Nga mice treated with Biostir AD, animal models of contact dermatitis and atopic dermatitis, respectively, was dose-dependently alleviated by administration of perampanel. These findings indicate that AMPA receptors play a crucial role in pruriceptive processing in mice with acute or chronic pruritus.

Free Research Field

精神神経科学

Academic Significance and Societal Importance of the Research Achievements

痒みは生活の質にも影響を及ぼす不快な感覚でありながら、健康障害としては軽視されてきた歴史的背景がある。近年、病的な痒みの重篤度が世界的に周知されるようになり、脳内報酬系との関与をはじめ、痒みの基礎研究も活発になってきたが、中枢神経系が深く関与している難治性痒みの発症メカニズムやその治療法は未だ解明されていない。本研究から、AMPA受容体がマウスの急性および慢性の痒みの情報伝達において重要な役割を果たしており、抗てんかん薬であるペランパネルがヒトの痒みを軽減する候補薬となる可能性が示唆された。いわゆるドラッグ・リポジショニング（既存薬再開発）の可能性を強く示唆する結果であると考える。