The study of carry-over effect of beta3 adrenagic receptor agonist

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16743
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Kyohda Yuki 札幌医科大学, 医学部, 助教 (90718024)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: β3アドレナリン受容体作動薬 / 抗コリン薬 / 過活動膀胱 / carry over effect / 排尿機能

Outline of Final Research Achievements

In clinical practice, it has been reported that β3-adrenergic receptor agonists for overactive bladder are often discontinued due to symptom improvement compared to anticholinergics. Therefore, we hypothesized that the therapeutic effects of β3-adrenergic receptor agonists would continue after the end of administration in pollakiuria model rats, that is, carry-over.Iliac artery endothelial injury rats (AI rats) were used as a pollakisuria model, but it was very difficult to create the model. It was not possible to prove that the treatment effect of β3-adrenergic receptor agonists was sustained. Considering the possibility of model selection failure, administration experiments were also conducted in rats with spontaneous hypertensive rat, known as an overactive bladder model, but the carry-over effect could not be proved.

Free Research Field

urinary function

Academic Significance and Societal Importance of the Research Achievements

腸骨内皮障害ラットを、抗コリン薬投与群、β3アドレナリン受容体作動薬投与群にわけて、それぞれ8週間の薬剤投与後、8週間の休薬期間を設けて排尿機能を評価した。残念ながら、β3アドレナリン受容体作動薬の効果が休薬後も引き継がれることは証明されなかった。高血圧自然発症ラットでも実験を行ったが、同様の結果であった。仮説が間違っていた可能性もあるが、そもそも過活動膀胱ラットモデルについて定まったものがなく、その作成や選択という点において、検討の余地があると思われる。とはいえ、現時点では、β3アドレナリン受容体作動薬の効果が休薬後も継続するとはいえず、休薬は推奨はされないと考えられた。