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 (10f) was found to be the most potent agent in potentiating glutamate, aspartate, or N-methyl-D-aspartate (NMDA) stimulated 45Ca2+ uptake at the NMDA receptor. The mechanism of action of 10f 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 10f are consistent with a selectivity of action at the NMDA receptor. Moreover, azetidine 10f 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 50 μM.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1561-1571 |
| Number of pages | 11 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 33 |
| Issue number | 6 |
| State | Published - 1990 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Organic Chemistry
Cite this
Synthesis and bioactivity of a new class of rigid glutamate analogues. Modulators of the N-methyl-D-aspartate receptor. / Kozikowski, Alan P.; Tückmantel, Werner; Reynolds, Ian J.; Wroblewski, Jarda T.
In: Journal of Medicinal Chemistry, Vol. 33, No. 6, 1990, p. 1561-1571.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synthesis and bioactivity of a new class of rigid glutamate analogues. Modulators of the N-methyl-D-aspartate receptor
AU - Kozikowski, Alan P.
AU - Tückmantel, Werner
AU - Reynolds, Ian J.
AU - Wroblewski, Jarda T.
PY - 1990
Y1 - 1990
N2 - 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 (10f) was found to be the most potent agent in potentiating glutamate, aspartate, or N-methyl-D-aspartate (NMDA) stimulated 45Ca2+ uptake at the NMDA receptor. The mechanism of action of 10f 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 10f are consistent with a selectivity of action at the NMDA receptor. Moreover, azetidine 10f 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 50 μM.
AB - 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 (10f) was found to be the most potent agent in potentiating glutamate, aspartate, or N-methyl-D-aspartate (NMDA) stimulated 45Ca2+ uptake at the NMDA receptor. The mechanism of action of 10f 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 10f are consistent with a selectivity of action at the NMDA receptor. Moreover, azetidine 10f 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 50 μM.
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M3 - Article
C2 - 2160533
AN - SCOPUS:0025316402
VL - 33
SP - 1561
EP - 1571
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 6
ER -