In vitro and in vivo evaluation of polymethylene tetraamine derivatives as NMDA receptor channel blockers |
| |
| Authors: | Ryotaro Saiki Yuki Yoshizawa Anna Minarini Andrea Milelli Chiara Marchetti Vincenzo Tumiatti Toshihiko Toida Keiko Kashiwagi Kazuei Igarashi |
| |
| Affiliation: | 1. Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan;2. Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan;3. Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Bologna, Italy;4. Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, Rimini, Italy;5. Faculty of Pharmacy, Chiba Institute of Science, Choshi, Japan |
| |
| Abstract: | The biological activities of six symmetrically substituted 2-methoxy-benzyl polymethylene tetraamines (1–4) and diphenylethyl polymethylene tetraamines (5 and 6) as N-methyl-d-aspartate (NMDA) receptor channel blockers, were evaluated in vitro and in vivo. Although all compounds exhibited stronger channel block activities in comparison to memantine in Xenopus oocytes voltage clamped at ?70 mV, only compound 2 (0.4 mg/kg intravenous injection) decreased the size of brain infarction in a photochemically induced thrombosis model mice at the same extent of memantine (10 mg/kg intravenous injection). Other compounds (1, 3, 4, 5 and 6) did not decrease the size of brain infarction significantly due to the limited injection doses. The present study suggests that compound 2 could represent a valuable lead compound to design low toxicity polyamines for clinical use against stroke. |
| |
| Keywords: | Polymethylene teraamine derivative NMDA receptor channel blocker |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
