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| Targets |
NMDA Receptor
PEAQX specifically targets the glutamate-binding site of the NMDA receptor, with marked preference for NR1/NR2A subunit combinations. Its binding is voltage-independent and competitive. The IC50 value for human NMDA receptors (hNMDAR 1A/2A) is 270 nM, while the IC50 for hNMDAR 1A/2B is 29.6 uM, representing ~110-fold selectivity over the NR2B subunit. This selectivity is highly species-specific, with rodent receptors showing different selectivity profiles. |
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| ln Vitro |
Similar caspase-3 activation is produced by PEAQX (3 μM), although NVP-AAM007 is almost three times more powerful [2].
In electrophysiological studies using hippocampal slices or cultured neurons, PEAQX selectively blocks NR2A-containing NMDA receptor-mediated currents with high potency. It shows NMDA receptor antagonism without affecting AMPA or kainate receptors. The compound is used to discriminate between NR2A- and NR2B-dependent forms of synaptic plasticity such as long-term potentiation (LTP) and long-term depression (LTD). In HEK293 cells expressing recombinant NMDA receptors, PEAQX concentration-dependently inhibits glutamate-induced calcium influx with an IC50 of 270 nM for NR1/NR2A but >30 uM for NR1/NR2B. |
| ln Vivo |
PEAQX (10–40 mg/kg) enhances cortical caspase-3 activity after subchronic treatment in a dose-dependent manner [2]. In contrast to saline pretreatment, PEAQX (10 and 20 mg/kg) increased locomotor activity in response to PCP challenge (4 mg/kg on PN28–35) [2]. Even with learning and memory impairment, PEAQX (10 mg/kg, i.p.) counteracts the effects of PRE084 on CaMKIV-TORC1-CREB and BDNF [3].
In vivo, PEAQX has shown efficacy in animal models of various neurological disorders. It exhibits anticonvulsant activity in seizure models. In rodent models of ischemic stroke, PEAQX reduces infarct size and improves neurological outcomes when administered within a therapeutic window. The compound is also used to explore the contributions of NR2A-containing receptors to pain processing in models of chronic pain. Its oral bioavailability makes it suitable for behavioral studies. |
| Enzyme Assay |
The protocol involves preparing a reaction mixture containing the human NMDA receptor subtype (NR1/NR2A or NR1/NR2B) expressed in cell membranes, radiolabeled ligand (3H-MK-801 or ¹2⁵I-MK-801), and varying concentrations (0.1 nM to 100 uM) of PEAQX tetrasodium hydrate in Tris-HCl buffer (pH 7.4). After incubation at room temperature for 60-90 minutes, the mixture is filtered through GF/B filters pre-soaked in 0.3% polyethylenimine to separate bound radioligand from free. The radioactivity on the filters is counted using a liquid scintillation counter. Nonspecific binding is measured in the presence of 100 uM unlabeled MK-801. Ki values are calculated using the Cheng-Prusoff equation. Alternatively, a fluorescence-based calcium influx assay can be used: HEK293 cells stably expressing NR1/NR2A are loaded with Fluo-4 AM (2 uM, 30 min, 37degC), then stimulated with 100 uM glutamate in the presence of varying PEAQX concentrations (1-10,000 nM). Fluorescence increase (ex/em = 485/535 nm) is measured every 2 seconds for 60 seconds. IC50 values are generated by curve-fitting.
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| Cell Assay |
Primary rat cortical or hippocampal neurons (DIV 12-14) are plated in 96-well plates (1×10⁵ cells/well). For neuroprotection assays, neurons are exposed to 100 uM NMDA plus 10 uM glycine in the presence of increasing concentrations of PEAQX (0.1-100 uM) for 5-10 minutes. After 24 hours, cell viability is assessed by LDH release assay or Hoechst/propidium iodide staining. For calcium imaging, neurons are loaded with Fura-2 AM (5 uM, 30 min) and placed on an inverted fluorescence microscope. NMDA (100 uM) is applied in the presence or absence of PEAQX, and the ratio of fluorescence at 340/380 nm (indicative of intracellular Ca2+ concentration) is recorded. For electrophysiology, whole-cell patch-clamp recordings are performed in voltage-clamp mode (holding potential -60 to -70 mV). PEAQX (1-10 uM) is applied via a fast perfusion system, and NMDA (100 uM)-evoked currents are measured. Selectivity is confirmed by comparing inhibition in the presence of an NR2B-selective antagonist (e.g., ifenprodil, 10 uM).
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| Animal Protocol |
Animal/Disease Models: Timed, day 14 pregnant female SD (Sprague-Dawley) rats[2].
Doses: 10, 20 or 40 mg/kg. Route of Administration: SC Experimental Results: demonstrated a sensitized locomotor response to PCP challenge on PN28-35. Animal/Disease Models: Timed , day 14 pregnant female SD (Sprague-Dawley) rats[2]. Doses: 4 mg/kg. Route of Administration: IP Experimental Results: Did not Dramatically increase locomotor activity in rats treated sub-chronically with PEAQX on PN7, 9 and 11. Animal/Disease Models: 11 -week old C57BL/6 mice[3]. Doses: 10 mg/kg. Route of Administration: IP. Experimental Results: Reversed the effect of PRE084 (F3,78 = 10.446, p<0.01). Male Sprague-Dawley rats (250-300 g) are used in cerebral ischemia models. Middle cerebral artery occlusion (MCAO) is performed using the intraluminal filament method (60 min occlusion, 24-72 h reperfusion). PEAQX tetrasodium hydrate (dissolved in 0.9% saline) is administered intraperitoneally (5-20 mg/kg) or intravenously (1-5 mg/kg) immediately after reperfusion or at 0, 2, 4 hours. Infarct volume is measured by TTC (2,3,5-triphenyltetrazolium chloride) staining of 2-mm coronal brain sections. Behavioral recovery is assessed by neurological deficit scores (Bederson scale), rotarod (motor coordination), and adhesive removal test (somatosensory function). For seizure models, mice (C57BL/6J) are injected with pentylenetetrazole (PTZ, 50 mg/kg, i.p.) and observed for 30 min for seizure onset, latency to stage 3 seizure, and mortality. PEAQX (10-50 mg/kg, i.p.) is given 30 min prior to PTZ. For chronic pain, rats receive intraplantar injection of complete Freund's adjuvant (CFA, 50 microL, 1 mg/mL) to induce inflammatory pain. Mechanical allodynia is assessed by von Frey filaments. PEAQX is given intrathecally (10-50 microg) or systemically. |
| ADME/Pharmacokinetics |
PEAQX is orally bioavailable in rats. Following oral administration (10 mg/kg), peak plasma concentrations are reached within 1-2 hours, with an estimated half-life of 2-4 hours. The absolute oral bioavailability is approximately 20-30% in rodents. In pharmacokinetic studies, intravenous administration shows a biphasic plasma decay, with a rapid distribution half-life (t1/2 alpha ~0.2 h) and a slower elimination half-life (t1/2 beta ~1-2 h). The volume of distribution is moderate (1-2 L/kg), suggesting extravascular distribution. Protein binding in rat plasma is about 70-80%. Metabolism occurs primarily via CYP450 enzymes (likely CYP3A4/2D6). The major route of elimination is hepatic metabolism followed by biliary excretion. Urinary excretion of unchanged drug accounts for <10% of the dose. For in vivo studies, the compound should be dissolved in 0.9% saline or 5% glucose and used within 2-4 hours after reconstitution. Light and temperature sensitivity is low.
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| Toxicity/Toxicokinetics |
In preclinical safety studies, PEAQX demonstrates a reasonable therapeutic window between doses needed for NMDA antagonism and those causing adverse effects. The most notable toxicity at high doses is behavioral: sedation, ataxia, and motor impairment, which are mechanism-based due to excessive NMDA receptor blockade in the cerebellum and motor cortex. At very high doses (e.g., >50 mg/kg i.p.), it may induce psychotomimetic effects (e.g., hyperlocomotion, stereotypy) and cognitive impairment. No significant hepatotoxicity, nephrotoxicity, or hematological changes are observed at therapeutic doses. Chronic high-dose studies are not available. For all experiments, appropriate dose-finding studies should be conducted to avoid motor side effects.
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| References |
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| Additional Infomation |
PEAQX (NVP-AAM077) was initially developed by Novartis as a potential therapeutic for stroke, traumatic brain injury (TBI), epilepsy, and neurodegenerative diseases. However, concerns regarding species-dependent selectivity (high affinity for human but lower for rodent NR2A), narrow therapeutic window, and on-target side effects (psychotomimetic) halted clinical development. It has not received regulatory approval. Today, PEAQX is widely used as a standard pharmacological tool to dissect NR2A subunit function in vitro and in vivo. PEAQX tetrasodium hydrate has superior water solubility compared to the free acid. The tetrasodium salt form is essential for preparing concentrated stock solutions (>100 mM in water). The compound is stable as a lyophilized powder for >2 years when stored at -20degC and protected from light; reconstituted solutions (aqueous) are stable for about 2 weeks at 4degC but should be aliquoted and frozen at -20degC for long-term storage (avoid multiple freeze-thaw cycles). PEAQX is structurally related to other competitive NMDA antagonists like D-AP5 and CGP 37849.
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| Molecular Formula |
C17H15BRN3NA4O6P
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| Molecular Weight |
560.15
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| Related CAS # |
PEAQX;459836-30-7
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| Appearance |
Light yellow to khaki solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O :~25.5 mg/mL (~45.52 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (178.52 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7852 mL | 8.9262 mL | 17.8524 mL | |
| 5 mM | 0.3570 mL | 1.7852 mL | 3.5705 mL | |
| 10 mM | 0.1785 mL | 0.8926 mL | 1.7852 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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