| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Targets |
The primary molecular target of (R)-Amisulpride is the serotonin 5-HT7 receptor, a G protein-coupled receptor that is widely expressed in the brain and involved in the regulation of mood, circadian rhythm, and cognition. (R)-Amisulpride acts as a high-affinity antagonist at the 5-HT7 receptor, with a Ki value of approximately 22-47 nM. In addition to its 5-HT7 activity, the compound displays lower affinity for dopamine D2 receptors (Ki ≈ 140 nM) and D3 receptors (Ki ≈ 13.9 nM). Thus, (R)-Amisulpride exhibits approximately 3- to 6-fold selectivity for 5-HT7 over D2 receptors, and about 3-fold selectivity over D3 receptors. This receptor binding profile distinguishes (R)-Amisulpride from its S-enantiomer, which has higher affinity for D2 and D3 receptors, and from the racemic amisulpride, which engages both dopaminergic and serotonergic targets. The compound also shows affinity for sigma receptors, which are involved in the modulation of neurotransmitter release.
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| ln Vitro |
In vitro, (R)-Amisulpride exhibits potent antagonism at the 5-HT7 receptor, as demonstrated in functional assays measuring receptor-mediated signaling. The compound inhibits 5-HT-induced cAMP accumulation in cells expressing the recombinant human 5-HT7 receptor, with an IC50 consistent with its binding affinity. In contrast to the racemic amisulpride, which has significant D2 receptor antagonist activity (Ki of 2.8 nM for D2 and 3.2 nM for D3), (R)-Amisulpride shows much weaker D2/D3 activity. This selectivity allows researchers to study 5-HT7-mediated effects without the confounding influence of D2 receptor blockade. In addition to its effects on cAMP signaling, (R)-Amisulpride has been shown to modulate other downstream pathways, including MAPK/ERK signaling, in a receptor-dependent manner. The compound's ability to selectively inhibit 5-HT7 receptors in vitro makes it a useful tool for dissecting the specific contributions of 5-HT7 signaling to neuronal function and behavior.
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| ln Vivo |
In vivo, (R)-Amisulpride has demonstrated antidepressant-like activity in rodent models of depression, including the forced swim test and the tail suspension test. In these assays, administration of (R)-Amisulpride reduces immobility time, indicating an antidepressant-like effect. The compound's efficacy in these models is attributed to its 5-HT7 receptor antagonism, as 5-HT7 knockout mice show similar behavioral changes. In addition to its antidepressant-like effects, (R)-Amisulpride has been studied for its potential to improve cognitive function and modulate sleep-wake cycles, consistent with the known roles of 5-HT7 receptors in these processes. The compound has also been investigated for its effects on metabolic parameters, as 5-HT7 receptors are involved in the regulation of energy homeostasis and insulin sensitivity. In preclinical models of metabolic syndrome, (R)-Amisulpride has shown beneficial effects on glucose tolerance and lipid metabolism, suggesting potential applications beyond psychiatry. The compound's oral bioavailability and brain penetration are sufficient to achieve target engagement in the central nervous system at reasonable doses.
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| Enzyme Assay |
The non-cellular assay for (R)-Amisulpride involves competitive radioligand binding to membrane preparations from cells expressing recombinant human receptors. For the 5-HT7 receptor, membranes are incubated with a fixed concentration of a radiolabeled 5-HT7 ligand (such as [³H]-LSD or [³H]-5-CT) and varying concentrations of (R)-Amisulpride. For dopamine D2 and D3 receptors, appropriate radioligands (such as [³H]-spiperone or [³H]-methylspiperone) are used. Incubations are performed at room temperature or 37°C for a defined period to reach equilibrium. Bound and free radioligand are separated by rapid filtration through glass fiber filters, and radioactivity is measured by liquid scintillation counting. Non-specific binding is determined in the presence of a saturating concentration of a reference antagonist (such as haloperidol for D2/D3 or methiothepin for 5-HT7). The binding affinity (Ki) values are calculated from competition curves using nonlinear regression analysis. The selectivity of (R)-Amisulpride is assessed by screening against a panel of other receptors, ion channels, and transporters to identify potential off-target interactions.
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| Cell Assay |
The cellular assay for (R)-Amisulpride uses cell lines stably expressing the human 5-HT7, D2, or D3 receptors. For 5-HT7 receptor functional assays, cells are seeded in multi-well plates and pre-incubated with forskolin to stimulate adenylyl cyclase activity. Cells are then treated with (R)-Amisulpride at various concentrations, followed by stimulation with a 5-HT7 receptor agonist (such as 5-carboxamidotryptamine or 5-HT). After a defined incubation period, intracellular cAMP levels are measured using a competitive immunoassay (such as ELISA or AlphaScreen). The inhibition of agonist-induced cAMP accumulation by (R)-Amisulpride is calculated, and IC50 values are determined from concentration-response curves. For D2 and D3 receptor functional assays, similar cAMP or other signaling readouts (such as β-arrestin recruitment) are used. Cytotoxicity is assessed in parallel to ensure that the observed effects are not due to non-specific cell toxicity. The selectivity of (R)-Amisulpride for 5-HT7 over D2/D3 receptors can be confirmed by comparing its potency in these different cellular assays.
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| Animal Protocol |
The in vivo animal studies for (R)-Amisulpride typically use rodent models of depression, such as the forced swim test (FST) or tail suspension test (TST). In the FST, mice or rats are placed in a cylinder of water from which they cannot escape, and the duration of immobility is recorded as a measure of despair-like behavior. (R)-Amisulpride is administered orally or intraperitoneally at various doses (typically 1-30 mg/kg) 30-60 minutes before the test. A reduction in immobility time compared to vehicle-treated controls indicates an antidepressant-like effect. In the TST, animals are suspended by the tail, and immobility is scored similarly. Positive controls such as imipramine or fluoxetine are included to validate the assay. In addition to behavioral tests, (R)-Amisulpride has been studied in models of cognitive function, such as the novel object recognition test or the Morris water maze, to assess its effects on learning and memory. In metabolic studies, the compound is administered to diet-induced obese mice or rats, and parameters such as body weight, food intake, glucose tolerance, and insulin sensitivity are measured. Brain and plasma concentrations of (R)-Amisulpride are measured to confirm target engagement and pharmacokinetic exposure.
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| ADME/Pharmacokinetics |
(R)-Amisulpride is orally bioavailable and exhibits good brain penetration, making it suitable for studies of central nervous system targets. The compound is soluble in chloroform and methanol and is hygroscopic, requiring storage in dry, dark conditions. It should be stored at 0-4°C for short-term use and at -20°C for long-term storage, protected from light and moisture to prevent degradation. The compound's pharmacokinetic properties, including half-life, clearance, and volume of distribution, have been characterized in preclinical species. As a small molecule with favorable physicochemical properties, (R)-Amisulpride achieves sufficient systemic exposure to engage its targets in the brain at the doses used in preclinical studies. The compound's metabolic stability and lack of significant CYP450 inhibition contribute to its favorable drug-like properties.
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| Toxicity/Toxicokinetics |
(R)-Amisulpride is generally well-tolerated in preclinical studies, with a favorable safety profile compared to the racemic mixture due to reduced D2-mediated side effects. Unlike typical antipsychotics that block D2 receptors and cause extrapyramidal symptoms, (R)-Amisulpride's selectivity for 5-HT7 over D2 receptors minimizes the risk of motor side effects. The compound does not produce catalepsy in rodent models, which is a common indicator of D2-mediated extrapyramidal liability. In repeated-dose toxicity studies, (R)-Amisulpride has shown no significant organ toxicity at the doses tested. The compound is not genotoxic in standard assays. However, as a research compound, comprehensive toxicological data beyond preclinical findings are limited, and the compound should be handled with appropriate laboratory safety precautions.
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| Additional Infomation |
(R)-Amisulpride is the R-enantiomer of amisulpride and is the primary active component in SEP-4199, which is being developed for the treatment of bipolar depression. The stereoselectivity of (R)-Amisulpride distinguishes it from its S-enantiomer (esamisulpride) and the racemic mixture. While amisulpride is an approved antipsychotic used in the treatment of schizophrenia and dysthymia, (R)-Amisulpride represents a more targeted approach to modulating serotonergic pathways. The compound's unique receptor binding profile makes it a valuable research tool for investigating the role of 5-HT7 receptors in mood regulation, cognition, sleep, and metabolism. In addition to its potential in psychiatry, (R)-Amisulpride has been investigated for metabolic disorders, including obesity and insulin resistance, based on the emerging role of 5-HT7 receptors in energy homeostasis. The compound continues to be studied in preclinical and clinical research settings.
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| Molecular Formula |
C17H27N3O4S
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| Molecular Weight |
369.478983163834
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| Exact Mass |
369.172
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| CAS # |
71675-90-6
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| PubChem CID |
5746246
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
558.9±50.0 °C at 760 mmHg
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| Flash Point |
291.8±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.546
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| LogP |
1.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
25
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| Complexity |
549
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| Defined Atom Stereocenter Count |
1
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| SMILES |
S(CC)(C1C(=CC(=C(C=1)C(NC[C@H]1CCCN1CC)=O)OC)N)(=O)=O
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| InChi Key |
NTJOBXMMWNYJFB-GFCCVEGCSA-N
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| InChi Code |
InChI=1S/C17H27N3O4S/c1-4-20-8-6-7-12(20)11-19-17(21)13-9-16(25(22,23)5-2)14(18)10-15(13)24-3/h9-10,12H,4-8,11,18H2,1-3H3,(H,19,21)/t12-/m1/s1
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| Chemical Name |
4-amino-N-[[(2R)-1-ethylpyrrolidin-2-yl]methyl]-5-ethylsulfonyl-2-methoxybenzamide
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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 : ~100 mg/mL (~270.65 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.77 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.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.08 mg/mL (5.63 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 saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: 2.08 mg/mL (5.63 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7065 mL | 13.5325 mL | 27.0651 mL | |
| 5 mM | 0.5413 mL | 2.7065 mL | 5.4130 mL | |
| 10 mM | 0.2707 mL | 1.3533 mL | 2.7065 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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