Abstract
A variety of derivatives of azetidine-2,4*dicarboxylic acid were synthesized and examined for their ability to stimulate 45Ca2+ uptake in cultures of cerebellar granule cells. Of the compounds tested, the cis-azetidine-2,4-dicarboxylic acid (lOf) was found to be the most potent agent in potentiating glutamate, aspartate, or N-methyl-D-a9partate (NMDA) stimulated 45Ca2+ uptake at the NMDA receptor. The mechanism of action of lOf was further investigated in [3H]MK-801 binding assays and [3H]GABA release from cultured embryonic rat forebrain neurons. All of the results from the functional studies of azetidine lOf are consistent with a selectivity of action at the NMDA receptor. Moreover, azetidine lOf appears to exhibit a dual type of action, behaving as a glutamate-like agonist at higher concentrations and as a positive modulator at concentrations below 50µM.
Original language | English (US) |
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Pages (from-to) | 1561-1571 |
Number of pages | 11 |
Journal | Journal of medicinal chemistry |
Volume | 33 |
Issue number | 6 |
DOIs | |
State | Published - 1990 |
Externally published | Yes |
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery