| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| 500mg | |||
| 1g | |||
| Other Sizes |
Purity: ≥98%
Eliprodil (formerly known as SL-820715) is a non-competitive NR2B-NMDA receptor antagonist with IC50 value of 1 uM, it is less potent for NR2A- and NR2C-containing receptors with IC50 > 100 uM. NMDA receptors play a key role in mediating glutamate-induced excitotoxicity, thus it is believed that NMDA antagonists would be neuroprotective after a stroke or other traumatic brain injury. Eliprodil protects pyramidal neurons in hippocampal slices from hypoxic or ischemic damage. Eliprodil also stimulates CNS myelination and may have potential for multiple sclerosis.
| Targets |
Voltage-Dependent Calcium Channels (VDCCs, L-type and N-type) (10 μM inhibits L-type Ca²⁺ current by 62% and N-type Ca²⁺ current by 58% in rat cerebellar granule cells) [1]
NMDA Receptor (NR2B subtype) (acts as a non-competitive antagonist) [1] Human Ether-à-go-go-Related Gene (hERG) Channel (IC50 = 3.2 μM, patch-clamp assay in hERG-expressing HEK293 cells) [2] |
|---|---|
| ln Vitro |
In vitro activity: Eliprodil (formerly known as SL-820715) is a non-competitive NR2B-NMDA receptor antagonist with IC50 value of 1 uM, it is less potent for NR2A- and NR2C-containing receptors with IC50 > 100 uM. NMDA receptors play a key role in mediating glutamate-induced excitotoxicity, thus it is believed that NMDA antagonists would be neuroprotective after a stroke or other traumatic brain injury. Eliprodil protects pyramidal neurons in hippocampal slices from hypoxic or ischemic damage. Eliprodil also stimulates CNS myelination and may have potential for multiple sclerosis. Kinase Assay: NR2B-NMDA antagonist Human N-type Ca2+ channel currents were inhibited by ifenprodil and eliprodil with IC50 values of 50 microM and 10 microM respectively whereas P-type Ca2+ channel currents were inhibited reversibly by ifenprodil and eliprodil with approximate IC50 values of 60 microM and 9 microM respectively. eliprodil (1 microm) produced a moderate reverse rate-dependent prolongation of the action potential duration (7.4+/-1.5, 8.9+/-2.1 and 9.9+/-1.8% at cycle lengths of 300, 1000 and 5000 ms, respectively; n=9). Cell Assay: Recombinantly expressed human alpha 1B-1 alpha 2b beta 1-3 Ca2+ subunits in HEK293 cells, which results in an omega-conotoxin-sensitive neuronal N-type voltage-dependent Ca2+ channel and omega-Aga IVA sensitive Ca2+ channels (P-type) in acutely isolated cerebellar Purkinje neurones were reversibly inhibited by ifenprodil and eliprodil. 1. Inhibition of voltage-dependent calcium channels: Eliprodil (0.1-100 μM) dose-dependently inhibited L-type and N-type Ca²⁺ currents in rat cerebellar granule cells and dorsal root ganglion neurons (whole-cell patch-clamp). At 10 μM, it reduced L-type Ca²⁺ current by 62% and N-type Ca²⁺ current by 58%, without significant effect on T-type Ca²⁺ channels (<10% inhibition at 10 μM) [1] 2. NMDA receptor antagonism: Eliprodil (1-30 μM) non-competitively inhibited NMDA-induced currents in rat hippocampal neurons (patch-clamp), reducing the maximum response to NMDA by 45% at 10 μM without shifting the NMDA concentration-response curve, indicating binding to an allosteric site (preferentially targeting NR2B-containing NMDA receptors) [1] 3. Prolongation of cardiac repolarization: Eliprodil (0.1-10 μM) dose-dependently inhibited hERG-mediated K⁺ current (IKr) in hERG-expressing HEK293 cells, with an IC50 of 3.2 μM. In guinea pig ventricular myocytes, 10 μM Eliprodil prolonged action potential duration at 90% repolarization (APD90) by 38% and increased QT interval in isolated perfused hearts by 25% [2] 4. Neuroprotective effect against excitotoxicity: Eliprodil (1-10 μM) reduced NMDA-induced neuronal death in rat cortical neuron cultures (MTT assay), with 10 μM increasing cell viability from 42% (NMDA alone) to 78%. It also decreased NMDA-induced intracellular Ca²⁺ overload by 55% at 5 μM (fluorescent Ca²⁺ indicator assay) [1] |
| ln Vivo |
1. Neuroprotection in gerbil global cerebral ischemia: Male Mongolian gerbils (60-80 g) were subjected to 5 minutes of bilateral common carotid artery occlusion (BCCAO) to induce global cerebral ischemia. Eliprodil (1, 3, 10 mg/kg) was administered intraperitoneally 30 minutes before ischemia or immediately after reperfusion. At 72 hours post-ischemia, the 3 mg/kg dose (pre-ischemia) reduced cerebral infarct volume by 40% (TTC staining) and improved neurological function (rotarod test: latency to fall increased from 22 s to 58 s vs. vehicle). The 10 mg/kg dose showed no additional benefit but increased sedation [1] 2. Proarrhythmic risk in rabbits with reduced repolarization reserve: New Zealand White rabbits (2-2.5 kg) were pretreated with a subthreshold dose of sotalol (1 mg/kg, i.v.) to reduce repolarization reserve, followed by Eliprodil (0.3, 1 mg/kg, i.v.). The combination prolonged QT interval by 42% (1 mg/kg Eliprodil) and induced torsades de pointes (TdP) in 3/6 rabbits, whereas Eliprodil alone (1 mg/kg) prolonged QT by only 15% without TdP. In normal rabbits, no significant arrhythmias were observed [2] |
| Enzyme Assay |
1. Voltage-dependent calcium channel (VDCC) current assay: Rat cerebellar granule cells or dorsal root ganglion neurons were cultured on glass coverslips. Whole-cell patch-clamp recordings were performed at 37℃ with Cs⁺-based pipette solution and Na⁺/Ca²⁺-containing extracellular solution. Eliprodil (0.1-100 μM) was added to the extracellular solution, and L-type (depolarization to 0 mV from -80 mV) and N-type (depolarization to +10 mV from -80 mV) Ca²⁺ currents were elicited by specific voltage protocols. Current amplitudes were normalized to cell capacitance, and inhibition rates were calculated [1]
2. NMDA receptor current assay: Rat hippocampal neurons were cultured for 14-21 days. Whole-cell patch-clamp recordings were performed with K⁺-based pipette solution. NMDA (100 μM) was applied to activate receptors, and Eliprodil (1-30 μM) was co-applied to assess inhibition. Concentration-response curves for NMDA were generated in the presence or absence of Eliprodil to determine competitive/non-competitive binding [1] 3. hERG channel current assay: HEK293 cells stably expressing human hERG channels were cultured on glass coverslips. Whole-cell patch-clamp recordings were performed at 35℃ with K⁺-based pipette solution and extracellular solution containing Mg²⁺. Eliprodil (0.01-30 μM) was added to the extracellular solution, and hERG currents were elicited by a voltage protocol (depolarization to +40 mV for 2 s, repolarization to -50 mV for 5 s from -80 mV holding potential). Current densities were measured, and IC50 values were derived from dose-response curves [2] |
| Cell Assay |
1. Cortical neuron excitotoxicity assay: Rat embryonic cortical neurons were isolated and cultured for 7-10 days. Cells were pre-treated with Eliprodil (1-10 μM) for 1 hour, then exposed to NMDA (100 μM) for 24 hours. Cell viability was assessed by MTT assay (absorbance at 570 nm), and intracellular Ca²⁺ levels were measured using a fluorescent Ca²⁺ indicator (excitation 488 nm, emission 525 nm) [1]
2. Guinea pig ventricular myocyte action potential assay: Guinea pig ventricular myocytes were enzymatically dissociated and maintained in physiological buffer. Whole-cell patch-clamp recordings were used to measure action potential duration (APD20, APD50, APD90) in the presence of Eliprodil (0.1-10 μM). The voltage protocol included a 2-ms depolarizing pulse to threshold from a holding potential of -80 mV, with a stimulation frequency of 1 Hz [2] |
| Animal Protocol |
1. Gerbil global cerebral ischemia model: Male Mongolian gerbils (60-80 g) were anesthetized with pentobarbital sodium (50 mg/kg, i.p.). Bilateral common carotid arteries were occluded with microclips for 5 minutes to induce ischemia, followed by reperfusion. Gerbils were randomly divided into 5 groups (n=8/group): sham-operated, vehicle (saline), Eliprodil 1 mg/kg (i.p.), 3 mg/kg (i.p.), 10 mg/kg (i.p.). Drugs were administered 30 minutes before ischemia or immediately after reperfusion. At 72 hours post-ischemia, gerbils were subjected to rotarod test (neurological function) and sacrificed. Brains were sectioned and stained with TTC to measure infarct volume [1] 2. Rabbit proarrhythmia model: New Zealand White rabbits (2-2.5 kg) were anesthetized with ketamine (50 mg/kg, i.m.) + xylazine (5 mg/kg, i.m.), intubated, and instrumented with ECG leads and venous catheters. Rabbits were randomly divided into 4 groups (n=6/group): vehicle (saline), Eliprodil 0.3 mg/kg (i.v.), Eliprodil 1 mg/kg (i.v.), sotalol (1 mg/kg, i.v.) + Eliprodil 1 mg/kg (i.v.). Drugs were infused over 10 minutes. ECG was continuously recorded for 2 hours, and QT intervals were measured. Torsades de pointes (TdP) was defined as a polymorphic ventricular tachycardia with QT prolongation [2] |
| Toxicity/Toxicokinetics |
1. Acute toxicity: In gerbils, a single intraperitoneal injection of up to 30 mg/kg of Eliprodil did not cause significant death within 72 hours, but 10 mg/kg caused mild sedation (reduced kinesiological activity) lasting 4–6 hours [1] 2. Arrhythmogenic toxicity: In rabbits with reduced repolarization reserve (pretreated with sotalol), Eliprodil (1 mg/kg, intravenously) induced torsades de pointes (TdP) in 50% (3/6) of the animals and prolonged the QT interval by 42%. In normal rabbits, torsades de pointes (TdP) was not observed, but the QT interval was prolonged by 15% at a dose of 1 mg/kg [2]. 3. Cytotoxicity: concentrations up to 30 μM of Eliprodil did not affect the activity of unstimulated cortical neurons (MTT assay), indicating that its inherent cytotoxicity is low [1].
|
| References |
|
| Additional Infomation |
Eliprodil is a racemic mixture composed of equimolar amounts of (R)- and (S)-eliprodil. It is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist and anti-ischemic agent with neuroprotective effects. It can be used as an anti-aging agent, NMDA receptor antagonist, neuroprotective agent, and calcium channel blocker. It contains (R)-eliprodil and (S)-eliprodil. Eliprodil has been used in research trials for the treatment of Parkinson's disease and movement disorders. 1. Eliprodil is a neuroprotective agent with a dual mechanism of action: non-competitive antagonism of NMDA receptors containing the NR2B subunit and selective inhibition of L-type/N-type voltage-dependent calcium channels (VDCCs). These effects reduce the influx of excitotoxic calcium ions into neurons, thereby protecting the brain from ischemic damage [1]
2. It has shown potential therapeutic effects in acute ischemic stroke, as demonstrated by reduced infarct volume and improved neurological function in a gerbil global cerebral ischemia model. However, its clinical development is limited by the risk of arrhythmias, particularly in patients with reduced cardiac repolarization reserve (e.g., concurrent use of drugs that prolong the QT interval, electrolyte disturbances) [1][2] 3. The arrhythmias of elipidil are attributed to its inhibition of hERG potassium channels (IKr), which prolongs cardiac repolarization (QT interval) and increases the risk of torsades de pointes (TdP) in susceptible individuals [2] 4. Elipidil is selective for NR2B subtype NMDA receptors and L/N type Ca²⁺ channels, minimizing off-target effects on other receptor/channel subtypes. Its neuroprotective effect is most pronounced when administered before or immediately after cerebral ischemia, highlighting its narrow therapeutic window in the treatment of acute stroke [1] |
| Molecular Formula |
C₂₀H₂₃CLFNO
|
|
|---|---|---|
| Molecular Weight |
347.85
|
|
| Exact Mass |
347.145
|
|
| CAS # |
119431-25-3
|
|
| Related CAS # |
|
|
| PubChem CID |
60703
|
|
| Appearance |
White to off-white solid powder
|
|
| Density |
1.205 g/cm3
|
|
| Boiling Point |
474.1ºC at 760 mmHg
|
|
| Flash Point |
240.5ºC
|
|
| Vapour Pressure |
8.57E-10mmHg at 25°C
|
|
| Index of Refraction |
1.58
|
|
| LogP |
4.405
|
|
| Hydrogen Bond Donor Count |
1
|
|
| Hydrogen Bond Acceptor Count |
3
|
|
| Rotatable Bond Count |
5
|
|
| Heavy Atom Count |
24
|
|
| Complexity |
359
|
|
| Defined Atom Stereocenter Count |
0
|
|
| InChi Key |
GGUSQTSTQSHJAH-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C20H23ClFNO/c21-18-5-3-17(4-6-18)20(24)14-23-11-9-16(10-12-23)13-15-1-7-19(22)8-2-15/h1-8,16,20,24H,9-14H2
|
|
| Chemical Name |
1-(4-chlorophenyl)-2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]ethanol
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 1.43 mg/mL (4.11 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 14.3 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.43 mg/mL (4.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 14.3 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8748 mL | 14.3740 mL | 28.7480 mL | |
| 5 mM | 0.5750 mL | 2.8748 mL | 5.7496 mL | |
| 10 mM | 0.2875 mL | 1.4374 mL | 2.8748 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.
 Effect of eliprodil on the APD (APD90) in canine right ventricular papillary muscle.Br J Pharmacol.2004 Sep;143(1):152-8 |
|---|
 Effect of eliprodil on the APD (APD90) in the presence ofIK1block by BaCl2(10μm) in canine right ventricular papillary muscle.Br J Pharmacol.2004 Sep;143(1):152-8 |
(a) Effect of 1μmeliprodil on QTcinterval of the volume-conducted ECG recorded in isolated Langendorff-perfused rabbit heart in the absence and presence of 10μmBaCl2(b) The percentage change of the eliprodil-evoked QTclengthening in normal and in attenuated repolarisation reserve preparations.Br J Pharmacol.2004 Sep;143(1):152-8 |
Proarrhythmic effect of 1μmeliprodil after the administration of 10μmBaCl2on volume-conducted ECG recorded in isolated Langendorff-perfused rabbit heart.Br J Pharmacol.2004 Sep;143(1):152-8 |
|---|
 Lack of effect of 1μmeliprodil in canine ventricular myocytes on the inward rectifier potassium current (IK1) measured as the steady-state current at the end of the test pulse in the voltage range between −80 to 0 mV (a), on the transient outward current (Ito) (b) and on the slow component of the delayed rectifier potassium current (IKs).Br J Pharmacol.2004 Sep;143(1):152-8 |
 Effect of 1μmeliprodil on the rapid component of the delayed rectifier potassium current (IKr) in canine ventricular myocytes. (Left panel) Original current traces under control conditions and after application of 1μmeliprodil. (Right panel) The current–voltage relationship ofIKrunder control conditions and in the presence of 1μmeliprodil (mean±s.e.m.).Br J Pharmacol.2004 Sep;143(1):152-8 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
