1. In vitro and in vivo evaluation of polymethylene tetraamine derivatives as NMDA receptor channel blockers
- Author
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Ryotaro Saiki, Yuki Yoshizawa, Anna Minarini, Kazuei Igarashi, Keiko Kashiwagi, Andrea Milelli, Toshihiko Toida, Vincenzo Tumiatti, Chiara Marchetti, Ryotaro Saiki, Yuki Yoshizawa, Anna Minarini, Andrea Milelli, Chiara Marchetti, Vincenzo Tumiatti, Toshihiko Toida, Keiko Kashiwagi, and Kazuei Igarashi
- Subjects
Clinical Biochemistry ,Xenopus ,NMDA receptor channel blocker ,Pharmaceutical Science ,Pharmacology ,Receptors, N-Methyl-D-Aspartate ,Biochemistry ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Memantine ,In vivo ,Drug Discovery ,Polyamines ,medicine ,Animals ,Channel blocker ,Molecular Biology ,Dose-Response Relationship, Drug ,Molecular Structure ,biology ,Chemistry ,Organic Chemistry ,Thrombosis ,biology.organism_classification ,Polymethylene tetraamine ,In vitro ,Disease Models, Animal ,Drug Design ,Molecular Medicine ,NMDA receptor ,Polymethylene teraamine derivative ,Lead compound ,medicine.drug - 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.
- Published
- 2013
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