| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
rD2 Receptor 5147 nM (Ki) rD4 Receptor 3.6 nM (Ki) Histamine H1 Receptor 7430 nM (Ki)
Sonepiprazole selectively targets the dopamine D4 receptor (D4R) with high affinity, exhibiting Ki values of 3.6 nM for the rat D4 receptor and 10.1 nM for the human D4.2 receptor. It displays over 100-fold selectivity for D4 over other dopamine receptor subtypes, including D1 (Ki: 6600 nM) and D2 (Ki: 5147 nM for rat D2). It also shows weak affinity for the histamine H1 receptor (Ki: 7430 nM). |
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| ln Vitro |
With more than 100-fold selectivity for the D4 receptor over other receptors, such as dopamine, serotonin, and adrenergic receptors, sonepiprazole demonstrates extremely selective binding to the D4 dopamine receptor[1].
In cell-free receptor binding assays, Sonepiprazole demonstrates high-affinity binding to recombinant D4 receptors with Ki values in the low nanomolar range. It exhibits potent antagonism at D4 receptors with an IC50 of 1.1 nM at the D2 receptor in certain assay formats. The compound shows no significant activity at serotonin or adrenergic receptors, confirming its high selectivity for the D4 subtype. In cellular functional assays, Sonepiprazole acts as a potent antagonist at D4 dopamine receptors, inhibiting D4-mediated signaling pathways. It effectively blocks dopamine-induced responses in cells expressing recombinant D4 receptors. The compound demonstrates functional selectivity by potently inhibiting D4-mediated cAMP production while showing minimal activity at D2 or D1 receptors. Its antagonistic activity is concentration-dependent, with potency correlating with its receptor binding affinity. |
| ln Vivo |
In vivo, Sonepiprazole prevents stress-induced cognitive deficits in monkey models. It completely blocks the behavioral sensitization response to amphetamine in rats when co-administered during pretreatment. Unlike D2 antagonists such as haloperidol, Sonepiprazole does not block the behavioral effects of amphetamine or apomorphine, suggesting that D4 receptors play a distinct role in psychostimulant-induced behavioral plasticity.
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| Enzyme Assay |
Cell-free receptor binding assays are performed using membrane preparations from cells expressing recombinant dopamine receptors. Radioligand displacement studies utilize [³H]-labeled ligands specific for each receptor subtype. Membranes are incubated with varying concentrations of Sonepiprazole and the appropriate radioligand, followed by filtration and scintillation counting to determine bound radioactivity. Ki values are calculated from competition binding curves using nonlinear regression analysis.
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| Cell Assay |
For cellular assays, cells stably or transiently expressing human or rat D4 receptors are cultured in appropriate media. Cells are pre-incubated with Sonepiprazole at various concentrations, then stimulated with dopamine or a D4-selective agonist. Functional responses such as cAMP accumulation or reporter gene activity are measured. IC50 values are determined by fitting concentration-response data to a sigmoidal dose-response equation.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies in rodent models indicate that Sonepiprazole is orally bioavailable and can penetrate the blood-brain barrier. In monkey studies, the compound demonstrates sufficient central nervous system exposure to produce cognitive effects. The compound is metabolized primarily via hepatic pathways, with the mesylate salt form showing improved solubility and bioavailability characteristics.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies indicate that Sonepiprazole is generally well-tolerated at pharmacologically active doses. The compound does not produce the extrapyramidal side effects typically associated with D2 receptor antagonists such as haloperidol. Long-term safety profiles are consistent with its high receptor selectivity, although comprehensive toxicological data remain limited as the compound was primarily developed as a research tool.
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| References |
[1]. Effectiveness of the selective D4 antagonist sonepiprazole in schizophrenia: a placebo-controlled trial. Biol Psychiatry. 2004 Mar 1;55(5):445-51.
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| Additional Infomation |
Sonepiprazole is a small molecule drug. The International Nonproprietary Name (INN) stem "-prazole" in its name indicates that sonepiprazole is a benzimidazole derivative anti-ulcer drug. The monoisotopic molecular weight of sonepiprazole is 401.18 Da.
See also: sonepiprazole mesylate (active ingredient). Sonepiprazole has been investigated in preclinical models for cognitive enhancement and stress-related disorders. Its unique D4 selectivity makes it a valuable pharmacological tool for studying D4 receptor function. The compound has not progressed to clinical trials as a therapeutic agent. It is available as the mesylate salt for research purposes. The compound is featured in the Handbook of Receptor Classification and Signal Transduction. |
| Molecular Formula |
C21H27N3O3S
|
|---|---|
| Molecular Weight |
401.52
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| Exact Mass |
401.177
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| CAS # |
170858-33-0
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| Related CAS # |
170858-34-1; 170857-36-0; 170858-33-0
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| PubChem CID |
133079
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| Appearance |
Typically exists as solid at room temperature
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| Vapour Pressure |
5.27E-15mmHg at 25°C
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| LogP |
3.944
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
593
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1=CC=C2C(=C1)CCO[C@H]2CCN3CCN(CC3)C4=CC=C(C=C4)S(=O)(=O)N
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| InChi Key |
WNUQCGWXPNGORO-NRFANRHFSA-N
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| InChi Code |
InChI=1S/C21H27N3O3S/c22-28(25,26)19-7-5-18(6-8-19)24-14-12-23(13-15-24)11-9-21-20-4-2-1-3-17(20)10-16-27-21/h1-8,21H,9-16H2,(H2,22,25,26)/t21-/m0/s1
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| Chemical Name |
4-[4-[2-[(1S)-3,4-dihydro-1H-isochromen-1-yl]ethyl]piperazin-1-yl]benzenesulfonamide
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| Synonyms |
Sonepiprazole; 170858-33-0; U-101387; Isochr-etpip-phso2NH2; sonepiprazol;
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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: 125 mg/mL (311.32 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.18 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 20.8 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 (5.18 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4905 mL | 12.4527 mL | 24.9054 mL | |
| 5 mM | 0.4981 mL | 2.4905 mL | 4.9811 mL | |
| 10 mM | 0.2491 mL | 1.2453 mL | 2.4905 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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