![Dizocilpine Maleate [(+)-MK 801 maleate]](/upload/0201/CgAGS12jNEiAZ-8yAAAjlahnIBU561.png)
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Purity: ≥98%
Dizocilpine Maleate [formerly (+)-MK-801)], the maleate salt of (+)dizocilpine, is a non-competitive antagonist of NMDA (N-Methyl-D-aspartate) receptors with a Kd of 37.2 nM in rat brain membranes. (+)-MK-801 acts as a potent anti-convulsant and likely has dissociative anesthetic properties, but it is not used clinically for this purpose due to the discovery of brain lesions, called Olney's lesions in test rats.
| Targets |
NMDA Receptor
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| ln Vitro |
In rat cerebral cortical membranes, [3H]dizocilpine maleate binds with NMDA receptors at a Kd of 37.2±2.7 nM[1]. N-Me-D-Asp-induced current blockade is progressive and long-lasting when dizocilpine maleate is used[3]. The NMDA-induced current is gradually suppressed by dizocilpine maleate. Even when Dizocilpine (MK-801) is applied for an extended period of time in the presence of NMDA, Mg2+ (10 mM) inhibits Dizocilpine from blocking the N-Me-D-Asp-induced current. In outside-out patches, dizocilpine inhibits NMDA-activated single-channel activity[3]. Dizocilpine maleate (less than 500 μM) suppresses LPS-induced microglia activation, which is accompanied by elevated Cox-2 protein expression in BV-2 cells. In BV-2 cells, dococilpine (MK-801; <500 μM) decreases microglial TNF-α production with an EC50 of 400 μM[4].
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| ln Vivo |
In animal modeling, dizocilpine maleate can be used to create models of schizophrenia.
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| Enzyme Assay |
The compound MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate)] is a potent anticonvulsant that is active after oral administration and whose mechanism of action is unknown. We have detected high-affinity (Kd = 37.2 +/- 2.7 nM) binding sites for [3H]MK-801 in rat brain membranes. These sites are heat-labile, stereoselective, and regionally specific, with the hippocampus showing the highest density of sites, followed by cerebral cortex, corpus striatum, and medulla-pons. There was no detectable binding in the cerebellum. MK-801 binding sites exhibited a novel pharmacological profile, since none of the major neurotransmitter candidates were active at these sites. The only compounds that were able to compete for [3H]MK-801 binding sites were substances known to block the responses of excitatory amino acids mediated by the N-methyl-D-aspartate (N-Me-D-Asp) receptor subtype. These comprised the dissociative anesthetics phencyclidine and ketamine and the sigma-type opioid N-allylnormetazocine (SKF 10,047). Neurophysiological studies in vitro, using a rat cortical-slice preparation, demonstrated a potent, selective, and noncompetitive antagonistic action of MK-801 on depolarizing responses to N-Me-D-Asp but not to kainate or quisqualate. The potencies of phencyclidine, ketamine, SKF 10,047, and the enantiomers of MK-801 as N-Me-D-Asp antagonists correlated closely (r = 0.99) with their potencies as inhibitors of [3H]MK-801 binding. This suggests that the MK-801 binding sites are associated with N-Me-D-Asp receptors and provides an explanation for the mechanism of action of MK-801 as an anticonvulsant[1].
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| Cell Assay |
Neurons were dissociated from the visual cortex of 2- to 6-day-old Long Evans rat pups and grown in culture for 5-43 days as described (21). Currents activated by excit-fory amino acids were measured in the whole-cell and outside-out patch-clamp configurations. Pipettes contained an internal solution (in mM) of 120 cesium methanesulfonate, 5 CsCI, 10 Cs2EGTA, 5 Mg(OH)2, 5 MgATP, 1 Na2GTP, and 10 Hepes (pH adjusted to 7.4 with CsOH). The external solution (in mM) was 160 NaCl, 2 CaC12, and 10 Hepes (pH 7.40). In whole-cell experiments, 300 nM tetrodotoxin and 10 kLM bicuculline methiodide were added to the external solution to suppress spontaneous activity. MK-801, the kind gift of Paul Anderson, was added from stock solutions of 2-50 mM in ethanol, stored at - 20'C. Final concentrations of ethanol were <0.1%. Cells or patches were bathed in control or agonist-containing external solution flowing from one of a linear array of 7-10 microcapillary tubes fed by gravity. Rapid solution changes were made by moving the array of tubes relative to the cell (whole-cell) or by moving the pipette relative to the tubes (patch). All experiments were done at 20-250C[3].
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| Additional Infomation |
Dizocilpine maleate is a maleate salt obtained by reaction of dizocilpine with one equivalent of maleic acid. It has a role as an anaesthetic, an anticonvulsant, a neuroprotective agent, a nicotinic antagonist and a NMDA receptor antagonist. It is a maleate salt and a tetracyclic antidepressant. It contains a dizocilpine(1+).
A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects. |
| Molecular Formula |
C20H19NO4
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| Molecular Weight |
337.3692
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| Exact Mass |
337.131
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| Elemental Analysis |
C, 71.20; H, 5.68; N, 4.15; O, 18.97
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| CAS # |
77086-22-7
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| Related CAS # |
(-)-Dizocilpine maleate;121917-57-5;Dizocilpine;77086-21-6
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| PubChem CID |
6420042
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| Appearance |
White to off-white solid powder
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| Boiling Point |
541ºC at 760 mmHg
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| Melting Point |
183-185ºC
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| Flash Point |
281ºC
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| LogP |
3.19
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
25
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| Complexity |
432
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@@]12C3=CC=CC=C3C[C@@H](N1)C4=CC=CC=C24.C(=C\C(=O)O)\C(=O)O
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| InChi Key |
QLTXKCWMEZIHBJ-BTJKTKAUSA-N
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| InChi Code |
InChI=1S/C16H15N.C4H4O4/c1-16-13-8-4-2-6-11(13)10-15(17-16)12-7-3-5-9-14(12)16;5-3(6)1-2-4(7)8/h2-9,15,17H,10H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1-
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| Chemical Name |
5-methyl-10,11-dihydro-5H-5,10-epiminodibenzo[a,d][7]annulene maleate
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| Synonyms |
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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. |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.41 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (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 25.0 mg/mL clear EtOH 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: ≥ 2.5 mg/mL (7.41 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (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 25.0 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.19 mg/mL (6.49 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.08 mg/mL (6.17 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 5: ≥ 2.08 mg/mL (6.17 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 6: 3.45 mg/mL (10.23 mM) in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9641 mL | 14.8205 mL | 29.6410 mL | |
| 5 mM | 0.5928 mL | 2.9641 mL | 5.9282 mL | |
| 10 mM | 0.2964 mL | 1.4821 mL | 2.9641 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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