| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg | |||
| Other Sizes |
| Targets |
CB1 receptor (inverse agonist/antagonist) [1]
CB2 receptor (antagonist) [1] |
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| ln Vitro |
In SH-SY5Y cells, AM281 (0.01-10 μM) causes neurotoxicity at concentrations that raise the presence of 10 μM Aβ 25-35 when combined with 10 μM KSO 1-6 [2].
AM281 was tested in a plate-based functional assay measuring receptor internalization in CHO cells stably expressing human CB1 or CB2 receptors. The IC50 values for inhibition of CB1 internalization (using [3H]-Win 55,212-2 as agonist) and CB2 internalization (using [3H]-CP55,940 as agonist) were determined. The normalized dose-response curves for CB1 and CB2 are presented (Fig. 2A and 2B). [1] For CB1 receptor, the IC50 value of AM281 was reported to be similar to previously published values. For CB2 receptor, the IC50 value showed less than ~3-fold difference compared to literature. The selectivity ratio (CB2/CB1) was consistent with literature. [1] |
| ln Vivo |
Both the chronic doses of AM281 (0.62, 1.25, and 2.5 mg/kg) and the chronic doses of AM281 (2.5, 5 and 10 mg/kg) showed improvements in memory performance and exploration time [3]. The recognition index was increased to 22.1±4.8 with long-term administration of 2.5 mg/kg AM281, and memory impairment was improved to 8.5±4 with a single dosage of 5 mg/kg AM281, as opposed to 4.8±2.5 with vehicle therapy. AM281 given continuously at a dose of 2.5 mg/kg and
AM281 (0.62, 1.25, 2.5 mg/kg, i.p., chronic administration concurrent with morphine for 3 days) significantly shortened the exploration time (T1) in the object recognition task during spontaneous morphine withdrawal in male NMRI mice. At 2.5 mg/kg, it improved the recognition index (RI) to 22.1 ± 4.8 compared to vehicle-treated group (4.8 ± 2.5). Lower doses (0.62 and 1.25 mg/kg) did not improve RI. [3] AM281 (2.5, 5, 10 mg/kg, i.p., acute administration 40 min before the second trial) at 5 mg/kg significantly augmented RI to 8.5 ± 4 compared to vehicle (4.8 ± 2.5), but did not reach saline control values. Doses of 2.5 and 10 mg/kg showed no effect on RI. [3] |
| Cell Assay |
CHO cells stably transfected with human CB1 or CB2 receptors were cultured in 96-well plates at a density of 2.0×10^5 cells/mL for 24 hours. To assess antagonist effects on CB1 internalization, cells were pre-incubated with two-fold serial dilutions of AM281 (20–20000 nM for CB1; 0.4–40000 nM for CB2) for one hour, followed by treatment with radiolabeled agonist ([3H]-Win 55,212-2 at 10 nM for CB1; [3H]-CP55,940 at 2 nM for CB2) for one hour. Cells were then washed twice with PBS, lysed with 1.0 N NaOH, and radioactivity was measured by liquid scintillation counting. Non-specific binding was determined using untransfected CHO-CAR cells and in the presence of antagonists. [1]
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| Animal Protocol |
Animal/Disease Models: Male NMRI mice weighing 25-30 g [3] Doses: 0.62, 1.25 and 2.5 mg/kg (chronic dose); rapid dose of 5 mg/kg Can improve memory[3]. 2.5, 5 and 10 mg/kg (acute administration) Dosing: intraperitoneally (ip) (ip) with morphine daily except on the day of the experiment (chronic administration); alone 40 minutes before the second test (acute administration)
Experimental Results: Coadministration of AM281 and morphine daily Dramatically shortened exploration time compared to morphine-dependent mice receiving vehicle. The acute administration dose is 5 mg/kg, and the recognition index is Dramatically enhanced. Male NMRI mice (25–30 g) were housed under controlled conditions (12 h light/dark cycle). Mice were made dependent on morphine by subcutaneous injection of increasing doses (30, 45, 60, 90 mg/kg) twice daily for 3 days. On the third day, the last morphine dose was given, and cognition was evaluated 4 hours later using the object recognition task. [3] AM281 was dissolved in 4% DMSO and 0.9% saline and injected intraperitoneally. For chronic treatment, AM281 (0.62, 1.25, 2.5 mg/kg) was administered concurrently with morphine every day for 3 days. For acute treatment, AM281 (2.5, 5, 10 mg/kg) was injected once 40 minutes before the second trial of the object recognition task. Control groups received saline or vehicle (DMSO/saline). [3] |
| References |
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| Additional Infomation |
1-(2,4-Dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-(4-morpholino)-3-pyrazole carboxamide is a pyrazole compound and a cyclic compound.
AM281 is a diarylpyrazole derivative developed as a selective CB1 cannabinoid receptor antagonist/inverse agonist. It was derived from Rimonabant by replacing the p-chlorophenyl group at position 5 with a p-iodophenyl moiety and replacing the piperidine group with a morpholino group. This modification resulted in a significant increase in selectivity for the CB1 receptor over CB2, with similar affinity for CB1. [1] Chronic administration of AM281 (2.5 mg/kg) during morphine dependence improved memory performance in the object recognition task, suggesting that activation of CB1 receptors contributes to memory impairment during spontaneous morphine withdrawal. Acute administration (5 mg/kg) also improved memory, while higher doses (10 mg/kg) had no effect, possibly due to anxiety-like effects. [3] |
| Molecular Formula |
C21H19N4O2CL2I
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|---|---|
| Molecular Weight |
557.21116
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| Exact Mass |
555.993
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| CAS # |
202463-68-1
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| PubChem CID |
4302962
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| Appearance |
White to light yellow solid powder
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| Density |
1.7±0.1 g/cm3
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| Index of Refraction |
1.706
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| LogP |
4.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
589
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(N(N=C1C(NN2CCOCC2)=O)C3=C(Cl)C=C(Cl)C=C3)C4=CC=C(I)C=C4
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| InChi Key |
AJFFBPZYXRNAIC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H19Cl2IN4O2/c1-13-19(21(29)26-27-8-10-30-11-9-27)25-28(18-7-4-15(22)12-17(18)23)20(13)14-2-5-16(24)6-3-14/h2-7,12H,8-11H2,1H3,(H,26,29)
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| Chemical Name |
1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-morpholin-4-ylpyrazole-3-carboxamide
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| Synonyms |
AM 281 AM-281 AM281
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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) |
DMSO : ~7.14 mg/mL (~12.81 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.71 mg/mL (1.27 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 7.1 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 | 1.7947 mL | 8.9733 mL | 17.9466 mL | |
| 5 mM | 0.3589 mL | 1.7947 mL | 3.5893 mL | |
| 10 mM | 0.1795 mL | 0.8973 mL | 1.7947 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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