Synthesis of a novel water-soluble NMDA receptor antagonist

• Published in: Journal of heterocyclic chemistry Vol. 45; no. 2; pp. 383 - 387
• Main Authors: Masuko, Takashi, Kusama, Tadashi, Nagaoka, Hiroki, Metori, Koichi, Kizawa, Yasuo, Miyake, Muneharu
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley-Blackwell 01-03-2008; Wiley‐Blackwell
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.5570450214

A novel water‐soluble N‐methyl‐D‐aspartate (NMDA) receptor antagonist ATGDMAP 1 as synthesized and the effect of 1 on NMDA receptors was studied using voltage‐clamp recordings of recombinant NMDA receptors expressed in Xenopus oocytes. The compound 1 inhibited macroscopic currents in NR1/NR2A, NR1/NR2B, NR1/NR2C and NR1/NR2D receptor subtypes in oocytes voltage‐clamped at ‐70 mV. Mutant NR1/NR2B receptors containing NR1(T648A) or NR1(T648S) had very large holding currents when voltage‐clamped at ‐70 mV compared to that of wild‐type NMDA receptors, because these mutants generate constitutively open channels. ATGDMAP 1 and Mg2+, a channel blocker of the NMDA receptor, reduced the large holding currents needed for mutant NMDA receptors. These data indicate that ATGDMAP 1 directly acts on the channel pores of the NMDA receptor.