Evaluation of the effects of a new series of SMTPs in the acetic acid-induced embolic cerebral infarct mouse model

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14958
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Showa University
• Principal Investigator: Shibata Keita 昭和大学, 薬学部, 准教授 (50727328)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 脳梗塞 / SMTPs / 血栓溶解薬 / プラスミン活性作用 / 抗炎症作用 / 抗酸化作用

Outline of Final Research Achievements

Tissue plasminogen activator (t-PA) has a short therapeutic time window for administration (4.5 h) and carries a risk of promoting intracerebral hemorrhage. The aim of the present study was to evaluate and compare the effect of a new series of SMTPs in the acetic acid-induced embolic cerebral infarct mouse model. Treatment with either SMTP-22 or SMTP-43 (10mg/kg), which have plasmin, anti-inflammatory and anti-oxidant activities, resulted in reduced infarct area, neurological score and edema. Coexistence of all these three activities appears to be important for the treatment of embolic infarction because SMTP-6, SMTP-25, and SMTP-44D (10mg/kg), which are each missing at least one of the three functions, were not as effective. Therefore, these results indicate that SMTP-22 and SMTP-43 have potential as medicinal compounds for the treatment of embolic cerebral infarction.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

脳梗塞の急性期治療において、既存薬であるt-PAのような発症後の投与時間制限がある薬剤しか存在しない現状を踏まえると、新規脳梗塞治療薬の候補化合物を見い出せたことは、臨床的に非常に意義深いことである。また、血栓溶解作用のみではなく、抗炎症作用や抗酸化作用を併せ持つことの重要性を示せたことも、学術的に意義深いことである。