Synthesis of water-soluble polyamine derivatives effective as N-methyl-D-aspartate receptor antagonists.
The novel water-soluble N-methyl-D-aspartate (NMDA) receptor antagonists, N-{4-[4-(4-Guanidinobutylamino)butylamino]butyl}-p-toluenesulfonamide trihydrochloride (1a, TsHSPMG), N-{4-[4-(4-Guanidinobutylamino)butylamino]butyl}butane-1-sulfonamide trihydrochloride (1b, BsHSPMG), N-{3-[4-(3-Guanidinopropylamino)butylamino]propyl}-p-toluenesulfonamide trihydrochroride (2a, TsSPMG) and N-{3-[4-(3-Guanidinopropylamino)butylamino]propyl}butane-1-sulfonamide trihydrochroride (2b, BsSPMG), were synthesized, and the effects of these polyamine derivatives on NMDA receptors were studied using voltage-clamp recordings of recombinant NMDA receptors expressed in Xenopus oocytes. Although spermine potentiates 153% and 310% of NMDA (NR1A/NR2B) receptors in the presence of saturated and unsaturated glycine, respectively, all the novel polyamine derivatives, TsHSPMG (1a), BsHSPMG (1b), TsSPMG (2a) and BsSPMG (2b), significantly inhibited NR1A/NR2B receptors in both conditions. The degree of NMDA receptor inhibition by TsHSPMG (1a) and BsHSPMG (1b) was stronger than that by TsSPMG (2a) and BsSPMG (2b).
School of Pharmacy, Nihon University.
Takashi
T
Masuko
Shuhei
S
Yoshida
Koichi
K
Metori
Yasuo
Y
Kizawa
Tadashi
T
Kusama
Muneharu
M
Miyake
D000818:Animals; D015870:Gene Expression; D009865:Oocytes / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D012995:Solubility; D014867:Water / Q000737:chemistry; D014981:Xenopus / Q000378:metabolism
D011073:Polyamines; D016194:Receptors, N-Methyl-D-Aspartate; D014867:Water