Adverse effects of varenicline on the neurovascular unit

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460236
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Fukuoka University
• Principal Investigator: Kataoka Yasufumi 福岡大学, 薬学部, 教授 (70136513)
• Co-Investigator(Kenkyū-buntansha): DOHGU Shinya 福岡大学, 薬学部, 准教授 (60399186) ; TAKATA Fuyuko 福岡大学, 薬学部, 助教 (70412575)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: バレニクリン / 血液脳関門 / 中枢性有害作用 / ニコチン性アセチルコリン受容体 / タイトジャンクション

Outline of Final Research Achievements

Smoking cessation therapy with varenicline is associated with the increased risk of suicide or attempted suicide and depression, although varenicline exerts antidepressant-like effects as a partial agonist at α4β2 and full agonist at α7 nicotinic acetylcholine receptor (nAChR). These neuropsychiatric events may be attributed to the dysfunction of the neurovascular unit with hyperpermeability of the blood-brain barrier (BBB). The aim of this study is to determine nAChR subtype as a target for varenicline-indcued BBB hyperpermeability. We found that (1) brain endothelial barrier was impaired by a long term exposure of the α7 nAChR agonist, (2) brain pericytes were the highest responsive cell type to the α7 nAChR stimulation in releasing the matrix metalloproteinase-9, and (3) brain pericytes enhanced the α7 nAChR agonist-induced brain endothelial hyperpermeability. These findings suggest that varenicline would induce BBB dysfunction by stimulating α7 nAChR.

Free Research Field

医療系薬学