Design and Synthesis of a Novel Water-Soluble NMDA Receptor Antagonist with a 1,4,7,10-TetraaZacyclododecane Group

Design and Synthesis of a Novel Water-Soluble NMDA Receptor Antagonist with a 1,4,7,10-TetraaZacyclododecane Group

Polyamines, especially spermine, inhibit N-methyl-D-aspartate (NMDA) receptors as open channel blockers. Two types of water-soluble NMDA receptor antagonist, ACCn (1) and TGCn (2), with a 1,4,7,10-tetraazacyclododecane cyclic polyamine group, were synthesized and the effects of both compounds on NMD...

Full description

Saved in:
Bibliographic Details
Published in:Chemical & Pharmaceutical Bulletin Vol. 53; no. 4; pp. 444 - 447
Main Authors: Takashi MASUKO, Koichi METORI, Yasuo KIZAWA, Tadashi KUSAMA, Muneharu MIYAKE
Format: Journal Article
Language:Japanese
Published: Pharmaceutical Society of Japan 2005
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Polyamines, especially spermine, inhibit N-methyl-D-aspartate (NMDA) receptors as open channel blockers. Two types of water-soluble NMDA receptor antagonist, ACCn (1) and TGCn (2), with a 1,4,7,10-tetraazacyclododecane cyclic polyamine group, were synthesized and the effects of both compounds on NMDA receptors were studied using voltage-clamp recordings of recombinant NMDA receptors expressed in Xenopus oocytes. These compounds inhibited macroscopic currents in both NR1/NR2A and NR1/NR2B receptor subtypes in oocytes voltage-clamped at -70 mV. Inhibition by the compounds of NR1/NR2A receptors were more prominent than that of NR1/NR2B receptors. The inhibitory effects of ACCn (1) on both NMDA receptors were more potent than those of TGCn (2).
ISSN:0009-2363