title: Design and synthesis of a novel water-soluble NMDA receptor antagonist with a 1,4,7,10-tetraazacyclododecane group.
abstract: 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).
authors.affiliation: College of Pharmacy, Nihon University, Chiba.
authors.forename: Takashi
authors.initials: T
authors.lastname: Masuko
authors.forename: Koichi
authors.initials: K
authors.lastname: Metori
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kizawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kusama
authors.forename: Muneharu
authors.initials: M
authors.lastname: Miyake
mesh_terms: D000818:Animals; D000080027:Cyclams; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014981:Xenopus
chemical_list: D000080027:Cyclams; D018691:Excitatory Amino Acid Antagonists; D006571:Heterocyclic Compounds; D007202:Indicators and Reagents; D016194:Receptors, N-Methyl-D-Aspartate; C038072:cyclen