CNQX or cyanquixaline (6-cyano-7-nitroquinoxaline-2,3-dione) is a competitive

AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate. There are several types of glutamatergic ...

kainate Kainic acid, or kainate, is an acid that naturally occurs in some seaweed. Kainic acid is a potent neuroexcitatory amino acid agonist that acts by activating receptors for glutamate, the principal excitatory neurotransmitter in the central nervo ...

receptor antagonist. Its chemical formula is C₉H₄N₄O₄. CNQX is often used in the

retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...

to block the responses of OFF-bipolar cells for

electrophysiology Electrophysiology (from Ancient Greek, Greek , ''ēlektron'', "amber" ee the Electron#Etymology, etymology of "electron" , ''physis'', "nature, origin"; and , ''-logy, -logia'') is the branch of physiology that studies the electrical propertie ...

recordings. CNQX is an antagonist of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs). A study of the effects of CNQX on vestibuloocular reflex adaptation was done on goldfish by injecting CNQX into the vestibulo-cerebullum. The injection before adaptation significantly decreased and at the highest doses, completely inhibited the acquisition of adaptive reflex gain increases and decreases during a three-hour training period. Baseline performance was not affected by the CNQX injections. Injections of CNQX at the end of the training period shows a rapid loss of gained vestibuloocular reflex adaptation when the goldfish remained stationary in the dark. Instead of injecting CNQX immediately after training, injection made one to two hours after the initiation of the training period showed no signs of altering performance. CNQX injections did not have long-term permanent effects on the goldfish's ability to be retrained 48-hours later and was comparable to a control group that was not subjected to CNQX injections. CNQX did not inhibit adaptive changes while the injection was administered.

Research applications

Excitatory synaptic transmission can be mediated through changing the responsiveness of

AMPA receptors The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synaptic transmission in the centr ...

. One common method of altering responsiveness is changing the number of AMPA receptors in the

postsynaptic membrane Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

through endocytosis. Various stimuli, including CNQX, have diverse effects on AMPA receptor internalization. Known to be a

competitive antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of r ...

of the AMPA/

kainate receptor Kainate receptors, or kainic acid receptors (KARs), are ionotropic receptors that respond to the neurotransmitter glutamate. They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a dru ...

, CNQX is used in studies investigating whether or not AMPA receptor endocytosis is ligand-dependent. In a culture of hippocampal neurons, CNQX partially inhibited AMPA receptor internalization that was stimulated by

. However, when the hippocampal neurons were treated with CNQX alone, AMPA receptor internalization still took place in both the soma and dendrites. APV (NMDA receptor antagonist) or nimodipine (voltage gated calcium channel blocker) were also not able to block this internalization, suggesting that receptor activation is not a requirement for AMPA receptor endocytosis. The type of AMPA receptors endocytosed as a result of CNQX stimulation can also be identified using CNQX. In HEK cells tagged with GluR subunits, CNQX stimulates the internalization of GluR1 and GluR2 receptors. The intracellular region conserved in both GluR1 and GluR2 on the GluR2 C-terminal tail was identified and deleted. Deletion of this segment resulted in a decrease in constitutive endocytosis of the GluR2 receptor in HEK cells, pinpointing the sequence determining this effect. CNQX is known to be a selective competitive antagonist for both AMPA receptors, which have an IC₅₀ value of 400 nM, and kainate receptors, which have an IC₅₀ value of 4 µM. It also noncompetitively inhibits NMDA receptors. CNQX is thus used to isolate GABA_A receptor mediated spontaneous inhibitory postsynaptic currents. The actions of CNQX on the frequency of spontaneous inhibitory postsynaptic currents are independent of their actions at ionotropic glutamate receptors. Although the EC₅₀ value of CNQX on the frequency of spontaneous inhibitory postsynaptic currents is similar to the IC₅₀ value on kainate receptors, the blockade of kainate receptors is not responsible for the actions of CNQX.

NBQX NBQX (2,3-dioxo-6-nitro-7-sulfamoyl-benzo uinoxaline) is an antagonist of the AMPA receptor. NBQX blocks AMPA receptors in micromolar concentrations (~10–20 μM) and also blocks kainate receptors. In experiments, it is used to counter glutam ...

is a

quinoxaline A quinoxaline, also called a benzopyrazine, in organic chemistry, is a heterocyclic compound containing a ring complex made up of a benzene ring and a pyrazine ring. It is isomeric with other naphthyridines including quinazoline, phthalazine a ...

derivative that is known to be more effective than CNQX in blocking kainate receptors, but there was not a large increase in the frequency of spontaneous inhibitory postsynaptic currents. Additionally, CNQX’s effects were not replicated by kynurenate (glutamate receptor antagonist) or NS-102 (selective kainate receptor blocker) since there was no increase in the frequency of spontaneous inhibitory postsynaptic currents. Furthermore, D-AP5 and 7-CIK did not affect the frequency of spontaneous inhibitory postsynaptic currents, proving that the action of NMDA receptors do not account for the effects of CNQX.

References

External links

Chemical structure
{{Ionotropic glutamate receptor modulators AMPA receptor antagonists Kainate receptor antagonists Nitriles Nitro compounds NMDA receptor antagonists Quinoxalines Lactams

Research applications

See also

References

Further reading

External links