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).
Masuko
Takashi
T
School of Pharmacy, Nihon University.
Yoshida
Shuhei
S
Metori
Koichi
K
Kizawa
Yasuo
Y
Kusama
Tadashi
T
Miyake
Muneharu
M
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