1. In vitro and in vivo evaluation of polymethylene tetraamine derivatives as NMDA receptor channel blockers.
- Author
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Saiki, Ryotaro, Yoshizawa, Yuki, Minarini, Anna, Milelli, Andrea, Marchetti, Chiara, Tumiatti, Vincenzo, Toida, Toshihiko, Kashiwagi, Keiko, and Igarashi, Kazuei
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POLYMETHYLENE , *METHYL aspartate receptors , *STILBENE , *XENOPUS , *THROMBOSIS , *INFARCTION - Abstract
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 −70mV, only compound 2 (0.4mg/kg intravenous injection) decreased the size of brain infarction in a photochemically induced thrombosis model mice at the same extent of memantine (10mg/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. [Copyright &y& Elsevier]
- Published
- 2013
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