AMPA (IC50 = 0.3 μM); kainate receptor (IC50 = 1.5 μM)[1]
AMPA/Kainate receptors (non-NMDA subtype of glutamate receptors). The study demonstrates a clear preference of CNQX for non-NMDA receptors. [1]
Non-NMDA type glutamate receptors, with higher affinity for the quisqualate receptor subtype compared to NMDA and kainate receptor subtypes (as referenced from binding studies). [2]
Non-NMDA subtype of excitatory amino acid receptors (specifically kainate and quisqualate/AMPA receptors). The study confirms its selectivity against NMDA receptors. [3]
CNQX is an antagonist of the AMPA/kainate subtype of ionotropic glutamate receptors. The text also notes that compounds in the quinoxalinedione series, including CNQX, have inhibitory activity at kainate receptors and have been reported to show affinity for the glycine site of the NMDA receptor. [4]

CNQX (FG9065; 2–5 μM) 避免快速和慢速 GABA 介导的海马切片灌注抑制，同时可逆地扩张 Schaffer 侧枝和丝状兴奋性突触后电位 (EPSP) [2]。当 CNQX (1-5 μM) 接地时，从具有舞蹈兴奋的腰节记录的 DR-VRR 单突触成分的幅度会降低 [3]。

---

在大鼠脊髓神经元的在体电生理记录中，电泳给予CNQX（从1 mM溶液中电泳释放）能大致同等程度地降低激动剂使君子酸和红藻氨酸诱导的兴奋性反应。例如，在一个神经元中，CNQX (20 nA) 降低了由使君子酸和红藻氨酸引起的放电频率增加。该效应起效和恢复迅速。相比之下，CNQX对N-甲基-DL-天冬氨酸（NMA，一种NMDA受体激动剂）诱导的兴奋反应几乎没有影响。研究指出，在降低使君子酸和红藻氨酸反应方面，CNQX的效力明显高于另一种化合物GAMS。[1]
讨论中引用的受体结合实验指出，与在[3H]AMPA结合分析中的抑制活性相比，CNQX对[3H]红藻氨酸结合（特别是在Ca2+敏感的高亲和力位点）的抑制作用相对较弱。这表明其在生理条件下的功能性拮抗作用可能主要涉及使君子酸（AMPA）受体。[1]
在大鼠海马脑片制备中，灌注CNQX (2-5 µM) 可完全且可逆地阻断CA1区谢弗侧支通路和CA3区苔藓纤维通路刺激诱发的兴奋性突触后电位。阻断作用迅速（4 µM CNQX约2分钟），恢复需要长达30分钟的冲洗。CNQX的突触阻断作用与记录神经元的膜电位、输入电阻或锋电位适应性的改变无关。[2]
CNQX (2-4 µM) 在消除突触兴奋的同时，不改变由GABA介导的快和慢抑制性突触后电位的幅度，表明其不影响前馈抑制通路。[2]
在CA3神经元的电压钳实验中，CNQX 在降低激动剂诱导的内向电流方面表现出选择性。使君子酸 (10 µM) 诱导的电流被4 µM CNQX降低至对照的56 ± 17%，被10 µM CNQX降低至32 ± 4%。NMDA (20 µM) 诱导的电流降低程度较小（暴露5分钟后，分别被4 µM和10 µM CNQX降低至对照的77 ± 14%和66 ± 11%）。红藻氨酸 (200 nM) 诱导的内向电流被10 µM CNQX轻微降低（降至对照的78 ± 17%）。相比之下，NMDA受体拮抗剂AP-5或AP-7 (50 µM) 可降低NMDA诱导的电流，但不影响使君子酸或红藻氨酸诱导的电流。CNQX对测试激动剂的拮抗效力顺序为使君子酸 > 红藻氨酸 = NMDA。[2]
在离体七鳃鳗脊髓制备中，浴槽施加CNQX (5 µM) 阻断了运动神经元中记录的复合单突触兴奋性突触后电位的快速、非NMDA受体介导成分。在含有生理浓度Mg²⁺的正常林格氏液中应用时，CNQX留下了一个较小、较慢的EPSP成分，该成分随后可被NMDA受体拮抗剂AP5阻断，这表明CNQX对非NMDA受体具有选择性。[3]
CNQX (剂量高达15 µM) 对由浴槽应用NMDA受体激动剂N-甲基-D,L-天冬氨酸 (NMA, 100 µM) 诱导的虚拟运动（一种运动模式）的节律或组织没有影响。[3]
在TTX和低Mg²⁺存在下，将激动剂压力注射到运动神经元上的实验显示，浴槽应用DNQX (5 µM) 阻断了了对红藻氨酸和AMPA的反应，但不影响对NMDA的反应。虽然在这个特定图表/实验中未直接测试CNQX，但文中将CNQX与DNQX归为一类，认为它们在阻断非NMDA突触传递方面具有相同的特异性。[3]

CNQX (FG9065; 2–5 μM) 避免快速和慢速 GABA 介导的海马切片灌注抑制，同时可逆地扩张 Schaffer 侧枝和丝状兴奋性突触后电位 (EPSP) [2]。通过配音从腰节记录的 DR-VRR 单突触分量的幅度大约被 CNQX (1 -5 μM) 降低[3]。
在无可卡因阶段的前 15 分钟，CNQX 二钠（FG9065 二钠；0.75–3 mg/kg；腹腔注射；测试前 20 分钟）剂量依赖性地减少可卡因反应的次数 [4]。保留试验前10分钟，可将CNQX二钠（0.5或1.25μg）双侧注入杏仁核或背侧海马，以部分降低训练后24小时大鼠低血压抑制性回避的表达。 0.5 μg 时，CNQX 二钠完全阻断通道 [5]。

---

七鳃鳗运动的运动模式是由兴奋性氨基酸神经传递激活和维持的。喹喔啉二酮6,7-二硝基喹喔啉-2,3-二酮（DNQX）和6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）是哺乳动物中枢神经系统中非N-甲基-D-天冬氨酸（NMDA）受体的强效选择性拮抗剂。在七鳃鳗中，这些化合物现在被证明可以阻断脊髓腹角神经元中诱发的快速兴奋性突触电位。它们选择性地拮抗对选择性红藻氨酸和奎司琼受体激动剂（红藻氨酸及α-氨基-3-羟基-5-甲基-4-异恶酮（AMPA））应用的反应，但不影响NMDA受体介导的反应。此外，研究表明，在用DNQX或CNQX阻断非NMDA受体后，NMDA受体的激活足以引发和维持假想运动。相反，用AMPA激活奎司特受体，而不是奎司特，会导致具有与红藻氨酸激活的特性非常相似的虚构运动[3]。

---

增加可卡因单位剂量在第一和第二间隔期间增加了反应，第一次CS的潜伏期缩短。根据FR4（FR7:S）时间表，CNQX在前15分钟无可卡因间隔期间以剂量依赖的方式减少了可卡因反应的数量，但在第二个间隔或会话的后半部分都没有影响可卡因反应。在运动活动测试中，与在第一个固定间隔内显著减弱反应的剂量相比，更高的CNQX剂量会减少饲养。
结论：这些结果表明，AMPA/红藻氨酸受体参与了可卡因寻求行为的介导，部分受可卡因相关线索的控制[4]。

---

使用恐惧强化惊吓范式研究了杏仁核中非N-甲基-D-天冬氨酸受体在条件性恐惧表达中的作用。在杏仁核基底外侧核植入双侧套管的大鼠在每2天接受10对视觉或听觉条件刺激，并伴有足部电击。第二天，他们在有或没有条件刺激的情况下通过诱发声惊吓反射进行测试，并分为具有同等增强水平的组。一两天后，在杏仁核内输注赋形剂或0.025、0.25或2.5微克6-氰基-7-硝基喹喔啉-2,3-二酮后，再次对大鼠进行测试。该药物剂量依赖性地阻断了两种感觉模式中强化惊吓的表达，表明杏仁核中非NMDA受体的激活对于条件性恐惧的表达是必要的[5]。

---

1. 全身性腹膜内注射 AMPA/红藻氨酸受体拮抗剂 CNQX（0.75、1.5 和 3 mg/kg）能剂量依赖性地减少大鼠在可卡因强化二阶程序下，第一个无药固定间隔期内的有效杠杆按压次数。这种抑制作用特定于初始的“可卡因寻求”阶段，因为在第一次可卡因输注后的第二个间隔期内的反应以及后续会话中自我给药的可卡因输注总次数并未受到影响。[4]
2. 在单独的自发活动性测试中，3 mg/kg IP 剂量的 CNQX 显著抑制了垂直活动（ rearing），但并未减少水平活动；事实上，它在特定时间段内增加了水平活动。3 mg/kg 剂量对可卡因寻求的减弱可能部分与运动功能损害效应有关，但能够减弱寻求行为的较低剂量并未显著影响 rearing。[4]

海马脑片与6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX，2-5微M）的超融合可逆地阻断了Schaffer侧支和苔藓纤维兴奋性突触后电位（EPSP），同时保留了快速和慢速γ-氨基丁酸（GABA）介导的抑制。膜电位、输入电阻和刺突调节没有改变。与红藻氨酸或N-甲基-D-天冬氨酸诱导的电流相比，CNQX在更大程度上减少了奎奎司特诱导的内向电流。我们认为CNQX可能是研究兴奋性氨基酸介导的突触传递的有用拮抗剂[2]。

Animal/Disease Models: Male Wistar rats, body weight 180-200 g[4] Doses: 0.75, 1.5 and 3 mg/kg
Route of Administration: IP; 20 minutes before test
Experimental Results: During the first 15 minutes cocaine-free interval, Reduces the number of cocaine (IV; 0.25 mg/infusion) responses in a dose-dependent manner

---

Electrophysiological experiments were performed on pentobarbital-anesthetized rats. Action potentials from single neurons in the spinal cord (dorsal horn) were recorded using the center barrel of seven-barreled microelectrodes filled with 3.6M NaCl. The outer barrels of the microelectrode contained drug solutions for ejection by electrophoresis (iontophoresis). Once a neuron was located, baseline excitatory responses were established by cyclical ejection of the agonists quisqualate, kainate, and NMA. CNQX was dissolved at a concentration of 1 mM in a 200 mM CaCl2 solution (pH adjusted to 9.8) for loading into a microelectrode barrel. It was then ejected near the recorded neuron using electrophoretic current (e.g., 20 nA) to study its effects on the agonist-induced neuronal firing rates.[1]
Transverse hippocampal slices (500 µm thick) were prepared from male Wistar rats (90-125 g). The slices were transferred to a submerged-type recording chamber and continuously superfused (2 ml/min) with oxygenated artificial cerebrospinal fluid (ACSF) at 33-34°C. The ACSF composition was (in mM): NaCl 126, KCl 3.5, MgCl2 1.3, NaH2PO4 1.2, CaCl2 2, NaHCO3 25, and glucose 11, gassed with 95% O2 / 5% CO2 to a pH of 7.3. For intracellular recording and voltage-clamp experiments, microelectrodes were used. CNQX was applied by bath superfusion at concentrations ranging from 2 to 10 µM. In some voltage-clamp experiments, tetrodotoxin (TTX, 1 µM) was used to block voltage-gated sodium channels, and microelectrodes were filled with 3 M CsCl to reduce potassium currents.[2]
Experiments were performed on adult river lampreys (Lampetra fluviatilis). For intracellular recordings and synaptic transmission studies, the spinal cord was completely isolated. For studies of fictive locomotion, pieces of spinal cord were left attached to the underlying notochord. Preparations were bathed in cooled (8-10°C) lamprey Ringer's solution. For some intracellular recording experiments, Mg²⁺ was omitted from the solution. In experiments involving agonist ejection, drugs (e.g., NMDA, kainate, AMPA) were pressure-ejected from a pipette positioned over the spinal cord. For bath application, drugs like CNQX, DNQX, NMA, or AMPA were added directly to the bathing Ringer's solution at specified concentrations (e.g., CNQX 5-15 µM). Ventral root activity was recorded with suction electrodes to monitor fictive locomotion.[3]
1. Cocaine Self-Administration and CNQX Testing: Male Wistar rats were trained to self-administer intravenous cocaine under a complex second-order schedule [FI15 min(FR7:S)] followed by a period under an FR4(FR7:S) schedule. After stable responding was established at a cocaine dose of 0.50 mg/infusion, the effects of CNQX were tested. CNQX (0, 0.75, 1.5, 3 mg/kg) was dissolved in distilled water and administered intraperitoneally (IP) at a volume of 1 ml/kg, 20 minutes before the start of the self-administration session. Doses were administered in a counterbalanced order (Latin square design) once per week.[4]
2. Locomotor Activity Test: Rats were habituated to test cages after vehicle injections. The effects of CNQX (0, 0.75, 1.5, 3 mg/kg IP) were examined 20 minutes after injection. Locomotor activity (horizontal and vertical movements detected by photocell beams) was recorded for 60 minutes. Testing followed a within-subjects Latin square design with at least two vehicle injection days separating different CNQX dose tests.[4]
3. Surgical Procedure: Rats were implanted with chronic jugular catheters under isoflurane anesthesia for intravenous drug delivery. Catheters were flushed daily with an antibiotic and heparinized saline to maintain patency and prevent infection.[4]

[1]. Quinoxalinediones: Potent Competitive non-NMDA Glutamate Receptor Antagonists. Science. 1988 Aug 5;241(4866):701-3.

[2]. Blockade of excitatory synaptic transmission by 6-cyano-7-nitroquinoxaline-2,3-dione(CNQX) in the hippocampus in vitro. Neurosci Lett. 1988 Sep 23;92(1):64-8.

[3]. CNQX and DNQX block non-NMDA synaptic transmission but not NMDA-evoked locomotion in lamprey spinal cord. Brain Res. 1990 Jan 8;506(2):297-302.

[4]. Attenuation of Cocaine-Seeking Behaviour by the AMPA/kainate Receptor Antagonist CNQX in Rats. Psychopharmacology (Berl). 2003 Feb;166(1):69-76.

[5]. Infusion of the non-NMDA receptor antagonist CNQX into the amygdala blocks the expression of fear-potentiated startle. Behav Neural Biol. 1993 Jan;59(1):5-8.

6-Cyano-7-nitroquinoxaline-2,3-dione is a quinoxaline derivative.
A potent excitatory amino acid antagonist with a preference for non-NMDA iontropic receptors. It is used primarily as a research tool.

---

CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) is identified in this study as a potent and selective antagonist for non-NMDA type glutamate receptors (specifically quisqualate/AMPA and kainate receptors), with minimal effect on NMDA receptor-mediated responses. It was used as a pharmacological tool to dissect the contributions of different excitatory amino acid receptor subtypes in synaptic transmission in the mammalian spinal cord. The development of CNQX and DNQX opened possibilities for studying quisqualate and kainate receptor subtypes.[1]
This study characterizes CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) as a potent, selective, and reversible antagonist of excitatory synaptic transmission in the hippocampus, which is mediated by non-NMDA glutamate receptors. Its ability to block synaptic EPSPs while sparing GABAergic inhibition and its preferential antagonism of quisqualate-induced currents over NMDA-induced currents suggest it is a useful pharmacological tool for studying excitatory amino acid-mediated synaptic transmission. The findings support the hypothesis that the transmitter for the Schaffer collateral and mossy fiber EPSPs acts primarily on quisqualate-type receptors.[2]
This study in the lamprey spinal cord confirms that CNQX is a potent and selective antagonist of synaptic transmission mediated by non-NMDA (kainate and quisqualate/AMPA) excitatory amino acid receptors, consistent with its actions in the mammalian CNS. A key finding is that blockade of non-NMDA receptors with CNQX does not disrupt "fictive locomotion" (the coordinated motor pattern for swimming) induced solely by NMDA receptor activation, indicating that NMDA receptor-mediated synaptic transmission is sufficient to coordinate this rhythmic motor activity. The study also notes that, unlike DNQX at very high concentrations (>10 µM), CNQX (up to 15 µM) did not disrupt NMDA-evoked locomotion, suggesting a cleaner pharmacological profile at the doses used, potentially due to less action at the glycine site of the NMDA receptor complex.[3]
1. CNQX (6-cyano-7-nitroquinoxaline-2,3-dione disodium) is a water-soluble AMPA/kainate receptor antagonist.[4]
2. The study suggests that AMPA/kainate receptors are involved in mediating cocaine-seeking behavior that is controlled, at least partly, by cocaine-associated environmental cues (conditioned stimuli). The effect of systemic CNQX was specific to the cue-controlled "seeking" phase before cocaine intake, not the "taking" phase after cocaine infusion.[4]
3. The article discusses that the neural circuit potentially involved includes glutamatergic projections from the anterior cingulate cortex and basolateral amygdala to the nucleus accumbens core.[4]

C₉H₄N₄O₄

232.15

232.023

115066-14-3

CNQX disodium;479347-85-8

3721046

White to yellow solid powder

1.7±0.1 g/cm3

659.3ºC at 760 mmHg

300 °C

352.6ºC

0.001mmHg at 25°C

1.699

0.64

135.33

2

5

0

17

434

0

RPXVIAFEQBNEAX-UHFFFAOYSA-N

InChI=1S/C9H4N4O4/c10-3-4-1-5-6(2-7(4)13(16)17)12-9(15)8(14)11-5/h1-2H,(H,11,14)(H,12,15)

7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile

FG9065; 6-CYANO-7-NITROQUINOXALINE-2,3-DIONE; 7-Nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-carbonitrile; 7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile; 6-Quinoxalinecarbonitrile, 1,2,3,4-tetrahydro-7-nitro-2,3-dioxo-; FG 9065; FG-9065;FG 9065

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~20 mg/mL (~86.15 mM)
H2O : < 0.1 mg/mL

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

---

注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

View More

注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

---

口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

View More

口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

---

注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。