| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 100mg | |||
| Other Sizes |
| Targets |
NMDA receptor (N-methyl-D-aspartate receptor).
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| ln Vitro |
Midafotel is a potent and competitive NMDA receptor antagonist with a Ki of 40 nM and an ED50 of 39 nM. It is centrally active following systemic administration. The compound causes intense stereotyped behaviors in animal models. It exhibits neuroprotective effects, reducing infarction volume in models of focal brain ischemia. Midafotel dramatically increases extracellular levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the striatum.
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| ln Vivo |
In trajectories, midafotel (15 mg/kg; i.p.) strongly produces stereotypical behaviors [2]. Infarction dose volume is reduced by midafotel (1.5, 4.5, or 15 mg/kg; intravenously administered; started 15 minutes before to MCA occlusion; additional as a continuous infusion of 1, 3, or 10 mg/kg/h);
Midafotel (15 mg/kg, i.p.) strongly produces stereotypical behaviors in adult female Wistar rats. The 4.5 mg/kg dose was most effective in reducing infarction volume in focal brain ischemia models. Midafotel (1.5, 4.5, or 15 mg/kg, i.v.) administered 15 minutes before middle cerebral artery occlusion, with additional continuous infusion (1, 3, or 10 mg/kg/h), reduced infarction volume. The compound induces typical PCP-like behavioral syndrome, including ataxia, hyperkinesia, head-shaking, stereotypic sniffing, face-washing, and grooming. |
| Enzyme Assay |
The in vitro receptor binding assay for NMDA receptor antagonism uses radioligand binding to rat brain membranes or recombinant NMDA receptors. Midafotel is incubated with the receptor preparation and a radiolabeled NMDA receptor ligand (e.g., [3H]MK-801 or [3H]CPP) at varying concentrations (typically 0.1 nM to 100 µM). After incubation, bound and free radioactivity are separated by filtration. The Ki value is calculated from competition binding curves. For functional antagonism, NMDA-induced depolarizations are measured in rat neocortical slice preparations.
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| Cell Assay |
In vitro cellular assays are performed using primary neuronal cultures or cell lines expressing NMDA receptors. Cells are pre-incubated with Midafotel at varying concentrations (0.1 nM to 100 µM) followed by NMDA stimulation. Intracellular calcium influx is measured using calcium-sensitive fluorescent dyes (e.g., Fluo-4). Neuroprotective activity is assessed by measuring cell viability (MTT or LDH release) following NMDA-induced excitotoxicity. The compound's effect on NMDA-induced depolarizations can be measured using electrophysiological techniques in neocortical slice preparations.
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| Animal Protocol |
Animal/Disease Models: Adult female Wistar rats[2]
Doses: 15 mg/kg Route of Administration: IP Experimental Results: Induced typical PCP-like behavioral syndrome The 4.5 mg/kg dose was most effective in focal brain stress[3]. Ataxia, hyperkinesia, and stereotyped behaviors, namely head-shaking, stereotypic sniffing, face-washing, and grooming, Dramatically increase extracellular levels of HVA and 5-HIAA in the striatum. In vivo efficacy is evaluated in rat models of focal brain ischemia (middle cerebral artery occlusion, MCAO). Adult female Wistar rats undergo MCAO, and Midafotel is administered intravenously (1.5, 4.5, or 15 mg/kg) starting 15 minutes before occlusion, with additional continuous infusion (1, 3, or 10 mg/kg/h). Infarction volume is measured by TTC staining 24 hours after occlusion. For behavioral studies, Midafotel (15 mg/kg, i.p.) is administered to rats, and stereotyped behaviors are scored using standardized behavioral rating scales. |
| ADME/Pharmacokinetics |
Midafotel has a molecular weight of 250.19 g/mol and molecular formula C8H15N2O5P. It is centrally active following systemic administration, indicating good blood-brain barrier penetration. The compound has a LogP of -7, indicating high hydrophilicity. Midafotel is soluble in aqueous solutions and should be stored as a powder at -20°C. It is supplied as a white to off-white solid powder with ≥98% purity.
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| Toxicity/Toxicokinetics |
No detailed toxicity data is publicly available for Midafotel. The compound was discontinued in Phase 3 clinical development for cognitive disorders. As an NMDA receptor antagonist, potential adverse effects may include psychotomimetic effects, cognitive impairment, and motor disturbances. Standard preclinical toxicology assessments would include genotoxicity, cardiac safety, and repeated-dose toxicity studies. The compound causes intense stereotyped behaviors in animal models at high doses, indicating potential central nervous system toxicity.
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| References |
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| Additional Infomation |
Midafotel belongs to the piperazine class of compounds. Its structure is a piperazine ring with a carboxyl group substituted at position 2R and a (1E)-1-phosphonopropyl-1-en-3-yl group substituted at position 4. It is an antagonist of the N-methyl-D-aspartate receptor (NMDAR) and was clinically developed by Novartis for the treatment of cognitive impairment and brain injury (this development has been discontinued). It exhibits activity as an NMDA receptor antagonist, neuroprotective agent, and anticonvulsant. Midafotel is a piperazine carboxylic acid, belonging to the monocarboxylic acid, phosphonate, olefin, and tertiary amine classes.
Midafotel is a research-grade NMDA receptor antagonist that was previously in clinical development by Novartis for cognitive impairment and brain injury, but this program was discontinued. It is not approved for clinical use and is available only for research purposes. The compound is also known as D-CPP-ene and SDZ-EAA 494. It belongs to the piperazine carboxylic acid class and has a phosphonate group. Midafotel is supplied as a solid with ≥98% purity. |
| Molecular Formula |
C8H15N2O5P
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|---|---|
| Molecular Weight |
250.1908
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| Exact Mass |
250.072
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| CAS # |
117414-74-1
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| PubChem CID |
6435801
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| Appearance |
White to off-white solid powder
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| LogP |
-7
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
16
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| Complexity |
326
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| Defined Atom Stereocenter Count |
1
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| SMILES |
P(/C=C/CN1CCNC(C(O)=O)C1)(O)(O)=O
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| InChi Key |
VZXMZMJSGLFKQI-ABVWVHJUSA-N
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| InChi Code |
InChI=1S/C8H15N2O5P/c11-8(12)7-6-10(4-2-9-7)3-1-5-16(13,14)15/h1,5,7,9H,2-4,6H2,(H,11,12)(H2,13,14,15)/b5-1+/t7-/m1/s1
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| Chemical Name |
(2R)-4-[(E)-3-phosphonoprop-2-enyl]piperazine-2-carboxylic acid
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| Synonyms |
SDZ-EAA-494; SDZ-EAA 494; D-CPP-ene
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9970 mL | 19.9848 mL | 39.9696 mL | |
| 5 mM | 0.7994 mL | 3.9970 mL | 7.9939 mL | |
| 10 mM | 0.3997 mL | 1.9985 mL | 3.9970 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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