Details

Autor(en) / Beteiligte

• Monahan, J B
• Biesterfeldt, J P
• Hood, W F
• Compton, R P
• Cordi, A A
• Vazquez, M I
• Lanthorn, T H
• Wood, P L

Titel

Differential modulation of the associated glycine recognition site by competitive N-methyl-D-aspartate receptor antagonists

Ist Teil von

• Molecular pharmacology, 1990-06, Vol.37 (6), p.780-784

Ort / Verlag

United States: American Society for Pharmacology and Experimental Therapeutics

Erscheinungsjahr

1990

Quelle

MEDLINE

Beschreibungen/Notizen

• The competitive N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonopentanoate and two other five-atom linkage (C-5) omega-phosphono-alpha-amino acid analogs reduced [3H]glycine binding, in a dose-dependent manner, to a maximum of 45-55%, whereas seven-atom linkage (C-7) analogs had significantly less effect. The IC50 of the C-5 antagonists for the inhibition of [3H]glycine binding closely paralleled their potency both in displacing NMDA-selective L-[3H]glutamate binding and in negatively modulating (+)-[3H]5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne maleate ([3H]MK-801) binding. Additionally, reduction of glycine binding by the C-5 antagonists was reversed by both NMDA receptor agonists and C-7 competitive NMDA antagonists, providing evidence that the site of action of these C-5 antagonists is the NMDA recognition site, resulting in indirect modulation of the glycine site. These data imply a functional coupling between the NMDA and associated glycine recognition sites and, furthermore, suggest a differential interaction of C-5 and C-7 competitive NMDA antagonists with the NMDA receptor complex.