Neuroprotection by Tosyl-Polyamine Derivatives through the Inhibition of Ionotropic Glutamate Receptors

Tosyl-polyamine derivatives such as N-{4-[4-(guanidinobu-tylamino)-butylamino]butyl}-4-methylbenzenesulfonamide tri-hydrochroride (TsHSPMG) have been found to strongly inhibit macroscopic currents through heteromeric N-methyl-D-aspartate (NMDA) receptors (NR1/NR2A, NR1/NR2B) and Ca2-permeable -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, suggest-ing that tosyl-polyamine derivatives penetrate deeply into th