The hippocampus is an important brain region that is involved in neurological disorders such as Alzheimer disease, schizophrenia, and epilepsy. Ionotropic glutamate receptors—namely, N-methyl-D-aspartate (NMDA) receptors (NMDARs), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors (AMPARs), and kainic acid (KA) receptors (KARs)—are well known to be involved in these diseases by mediating long-term potentiation, excitotoxicity, or both. NBQX is an antagonist of AMPARs and KARs. NBQX for AMPA and KA stimulation (IC50 = 0.7 ± 0.1 and 0.7 ± 0.03 μM, respectively; n = 3). The effects of NBQX on the AMPA- or KA-evoked calcium rise in differentiated HIP-009 cells were assessed. NBQX inhibited both AMPA- and KA-induced signals in a concentration-dependent fashion (IC50 = 0.7 ± 0.1 and 0.7 ± 0.03 μM for AMPA and KA stimulation, respectively, n = 3). The AMPA-evoked calcium rise was completely inhibited by NBQX, whereas 68.6% ± 1.3% inhibition of the KA-induced signal was observed with 30 μM of NBQX treatment. The effect of co-treatment with MK-801 (a NMDAR antagonist) and NBQX on the glutamate-evoked calcium rise was assessed. When 30 μM of MK-801 or NBQX was added alone, 44.5% ± 2.2% or 34.2% ± 5.0%, respectively, of the glutamate-induced calcium rise was inhibited. Co-treatment had an additive inhibitory effect on total calcium rise upon glutamate stimulation (78.6% ± 2.2% inhibition)[1].
NBQX 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HEK293T cells
50 µM
4 hours
Competitive inhibition of CAM2(TCO) labeling to AMPARs
Nat Commun. 2021 Feb 5;12(1):831
Primary cortical neurons
50 µM
10 hours
Competitive inhibition of CAM2(TCO) labeling to endogenous AMPARs
Nat Commun. 2021 Feb 5;12(1):831
Hippocampal slice culture neurons
10 µM
14 days
To record NMDAR-mediated excitatory postsynaptic currents (NMDAR EPSCs), results showed complete elimination of NMDAR EPSCs in CRISPR/Cas9 transfected cells.
Neuron. 2014 Sep 3;83(5):1051-7
Human primary osteoblasts (HOBs)
200 µM
20 days
To evaluate the effects of NBQX on the number and mineralization of human primary osteoblasts. NBQX treatment reduced cell number and prevented mineralization.
Ann Rheum Dis. 2015 Jan;74(1):242-51
NBQX 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
AMPA- or NMDA-induced lethal convulsions model
Intraperitoneal injection
18.0 mg/kg (NMDA), 17.0 mg/kg (AMPA)
Single dose, observed 5 minutes after administration
Evaluate the protective effect of NBQX against AMPA- or NMDA-induced lethal convulsions
Br J Pharmacol. 1998 Nov;125(6):1258-66
Lewis rats
Antigen-induced arthritis (AIA) model
Intra-articular injection
2.5 mM
Single injection, observed for 21 days
To evaluate the effects of NBQX on joint swelling, inflammation, and degeneration in the AIA rat model. NBQX significantly reduced joint swelling (33%), inflammation scores (34%), and degeneration scores (27%).
Ann Rheum Dis. 2015 Jan;74(1):242-51
Long-Evans rats
Hypoxia-induced neonatal seizure model
Intraperitoneal injection
20 mg/kg
Every 12 hours for 4 doses
NBQX treatment significantly attenuated seizure-induced increases in p-P70S6K in the hippocampus and cortex, reduced the frequency of spontaneous recurrent seizures in adulthood, decreased aberrant mossy fiber sprouting in the CA3 region of the hippocampus, and restored preference for social novelty.
Epilepsia. 2013 Nov;54(11):1922-32
Rats
3NP-induced striatal neurodegeneration
Subcutaneous injection
24 mg/kg/day
Continuous for 28 days
NBQX attenuated the toxicity of 3NP, reducing the loss of striatal neurons
Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12885-90
Mice
Maximal electroshock seizures (MES) and pentylenetetrazol (PTZ)-induced seizure models
Intraperitoneal injection
80-120 mg/kg
Single administration, threshold determined 15 minutes later
NBQX significantly increased the threshold for electroshock and PTZ-induced seizures, but only at doses causing sedation and ataxia.
Br J Pharmacol. 1994 Dec;113(4):1349-57
C57BL/6J mice
TMEV-induced seizure model
Intraperitoneal injection
approximately 22.5 mg/kg twice daily
Twice daily, from day 2.5 to day 10.5 post infection
NBQX treatment significantly increased the number of mice experiencing seizures, the number of seizures per mouse, the cumulative seizure score per mouse, and the mortality rate.
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