NDLI: Neuroprotection by tosyl-polyamine derivatives through the inhibition of ionotropic glutamate receptors.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Masuko, Takashi Namiki, Rie Nemoto, Yuta Miyake, Muneharu Kizawa, Yasuo Suzuki, Toyofumi Kashiwagi, Keiko Igarashi, Kazuei Kusama, Tadashi
Description	Country affiliation: Japan Author Affiliation: Masuko T ( College of Pharmacy, Nihon University, Funabashi, Chiba, Japan. kusama.tadashi@nihon-u.ac.jp)
Abstract	Tosyl-polyamine derivatives such as N-{4-[4-(guanidinobutylamino)-butylamino]butyl}-4-methylbenzenesulfonamide trihydrochroride (TsHSPMG) have been found to strongly inhibit macroscopic currents through heteromeric N-methyl-D-aspartate (NMDA) receptors (NR1/NR2A, NR1/NR2B) and Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (homomeric glutamate receptor 1) receptors expressed in Xenopus laevis oocytes on voltage-clamp recording. In the present study, it was found that the inhibition of NMDA receptor activity induced by tosyl-polyamine derivatives was voltage-dependent. Some mutations located in the intracellular region of the channel pore, such as NR1 E621Q and NR2B W607L, reduced the inhibition by tosyl-polyamine derivatives, suggesting that tosyl-polyamine derivatives penetrate deeply into the channel pore of NMDA receptors. The neuroprotective effects of tosyl-polyamine derivatives against cell injury caused by NMDA were investigated in cultured rat hippocampal neurons. Addition of 1 microM TsHSPMG to medium ablated the neurotoxicity induced by NMDA, and a similar effect was observed with 30 microM memantine. The neuroprotective effects of tosyl-polyamine derivatives on NMDA-induced seizures in mice were also assayed. Intracerebroventricular or intravenous injection of TsHSPMG (0.1 or 0.5 mg/kg) decreased the seizures induced by intraperitoneal injection of NMDA in mice. These findings indicate that tosyl-polyamine derivatives exhibit neuroprotective effects not only in primary cultured neurons but also in mice.
File Format	HTM / HTML
ISSN	00223565
Issue Number	2
Volume Number	331
Journal	Journal of Pharmacology and Experimental Therapeutics
e-ISSN	15210103
Language	English
Publisher	American Society for Pharmacology and Experimental Therapeutics
Publisher Date	2009-11-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Neuroprotective Agents Research Support, Non-u.s. Gov't Excitatory Amino Acid Agonists Toxicity Humans Cytology Electrophysiology Neuroblastoma Polyamines Discipline Pharmacology N-methylaspartate Antagonists & Inhibitors Oocytes Journal Article Cloning, Molecular Patch-clamp Techniques Tosyl Compounds Female Seizures Receptors, Glutamate Neurons Prevention & Control Cells, Cultured Rats Receptors, N-methyl-d-aspartate Pharmacology Xenopus Laevis Metabolism Drug Effects Dansyl Compounds Chemically Induced Pregnancy Chemistry Animals Spermine Discipline Therapeutics Anthraquinones Cell Line, Tumor Mice Excitatory Amino Acid Antagonists Receptors, Ampa Hippocampus Analogs & Derivatives
Content Type	Text
Resource Type	Article
Subject	Molecular Medicine Pharmacology

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