Subtype-Specific Agonists for NMDA Receptor Glycine Binding Sites
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Subtype-Specific Agonists for NMDA Receptor Glycine Binding Sites. / Maolanon, Alex R.; Risgaard, Rune; Wang, Shuang Yan; Snoep, Yoran; Papangelis, Athanasios; Yi, Feng; Holley, David; Barslund, Anne F.; Svenstrup, Niels; Hansen, Kasper B.; Clausen, Rasmus P.
In: ACS Chemical Neuroscience, Vol. 8, No. 8, 16.08.2017, p. 1681-1687.Research output: Contribution to journal › Letter › Research › peer-review
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TY - JOUR
T1 - Subtype-Specific Agonists for NMDA Receptor Glycine Binding Sites
AU - Maolanon, Alex R.
AU - Risgaard, Rune
AU - Wang, Shuang Yan
AU - Snoep, Yoran
AU - Papangelis, Athanasios
AU - Yi, Feng
AU - Holley, David
AU - Barslund, Anne F.
AU - Svenstrup, Niels
AU - Hansen, Kasper B.
AU - Clausen, Rasmus P.
PY - 2017/8/16
Y1 - 2017/8/16
N2 - A series of analogues based on serine as lead structure were designed, and their agonist activities were evaluated at recombinant NMDA receptor subtypes (GluN1/2A-D) using two-electrode voltage-clamp (TEVC) electrophysiology. Pronounced variation in subunit-selectivity, potency, and agonist efficacy was observed in a manner that was dependent on the GluN2 subunit in the NMDA receptor. In particular, compounds 15a and 16a are potent GluN2C-specific superagonists at the GluN1 subunit with agonist efficacies of 398% and 308% compared to glycine. This study demonstrates that subunit-selectivity among glycine site NMDA receptor agonists can be achieved and suggests that glycine-site agonists can be developed as pharmacological tool compounds to study GluN2C-specific effects in NMDA receptor-mediated neurotransmission.
AB - A series of analogues based on serine as lead structure were designed, and their agonist activities were evaluated at recombinant NMDA receptor subtypes (GluN1/2A-D) using two-electrode voltage-clamp (TEVC) electrophysiology. Pronounced variation in subunit-selectivity, potency, and agonist efficacy was observed in a manner that was dependent on the GluN2 subunit in the NMDA receptor. In particular, compounds 15a and 16a are potent GluN2C-specific superagonists at the GluN1 subunit with agonist efficacies of 398% and 308% compared to glycine. This study demonstrates that subunit-selectivity among glycine site NMDA receptor agonists can be achieved and suggests that glycine-site agonists can be developed as pharmacological tool compounds to study GluN2C-specific effects in NMDA receptor-mediated neurotransmission.
KW - d -cycloserine
KW - d -serine
KW - Ionotropic glutamate receptor
KW - NMDA
KW - subtype selectivity
KW - superagonist
U2 - 10.1021/acschemneuro.7b00117
DO - 10.1021/acschemneuro.7b00117
M3 - Letter
C2 - 28514141
AN - SCOPUS:85027413593
VL - 8
SP - 1681
EP - 1687
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
SN - 1948-7193
IS - 8
ER -
ID: 183858151