| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg | |||
| Other Sizes |
Lusaperidone (R107474; R-107474; R 107474) is a potent α2 adrenergic receptor antagonist with Kis of 0.13 and 0.15 nM for α2A and α2C, respectively.
| Targets |
α2A adrenergic receptor ( Ki = 0.13 nM ); α2C adrenergic receptor ( Ki = 0.15 nM )
- α₂-adrenoceptors (including hα₂A, hα₂B, hα₂C subtypes): R107474 has subnanomolar affinity for hα₂A-adrenoceptors (Ki = 0.13 nM) and hα₂C-adrenoceptors (Ki = 0.15 nM), nanomolar affinity for hα₂B-adrenoceptors (Ki = 1 nM) [1] - 5-hydroxytryptamine₇ (h5-HT₇) receptors: R107474 shows nanomolar affinity (Ki = 5 nM) [1] - Other receptors: R107474 interacts weakly with dopamine receptors (hD₂L, hD₃, hD₄) and other 5-HT subtypes (h5-HT₁D, h5-HT₁F, h5-HT₂A, h5-HT₂C, h5-HT₅A) with Ki values ranging from 81 to 920 nM [1] |
|---|---|
| ln Vitro |
Lusaperidone exhibits nanomolar affinity for the hα2B adrenergic receptor and h5-HT7 receptors (Ki=1 and 5 nM, respectively), and subnanomolar affinity for the α2A and α2C adrenergic receptor (Ki=0.13 and 0.15 nM, respectively). Lusaperidone has a weak interaction (Ki values between 81 and 920 nM) with the following receptor types: dopamine-hD2L, -hD3 and -hD4, h5-HT1D, h5-HT1F, h5-HT2A, h5-HT2C, and h5-HT5A. In this study, lusomidine was tested up to 10 μM and found to interact with any of the other receptor or transporter binding sites only at micromolar concentrations or not at all. Lusaperidone is a full antagonist on both receptor subtypes and has been demonstrated to reverse the clonidine-induced inhibition of cyclic AMP production mediated by human α2A and α2C adrenoceptors expressed in cell lines (Kb is 2.8 and 4.4 nM, respectively)[1].
1. Receptor binding assays: R107474 was tested for its ability to inhibit binding to a panel of neurotransmitter receptors, drug receptors, ion channels, peptide receptors, and monoamine transporters using membrane preparations from brain tissue or cells expressing cloned human receptors. When tested up to 10 μM, R107474 only interacted with the aforementioned receptors (α₂-adrenoceptors, h5-HT₇, dopamine receptors, and partial 5-HT subtypes) and showed no interaction or interaction only at micromolar concentrations with other tested receptors/transporters [1] |
| ln Vivo |
Lusaperidone has an ED50 of 0.014 mg/kg sc (0.009-0.019) for α2A and 0.026 mg/kg sc (0.022-0.030) for α2C adrenergic receptors. After being administered intravenously in vivo, R107474 is absorbed very quickly; in the majority of tissues, including the brain, its maximum concentration is reached five minutes after the tracer injection[1].
1. α₂-adrenoceptor occupancy assay: After subcutaneous (sc) administration of R107474 to animals, ex vivo autoradiography was performed at 1 hour post-administration to measure α₂A- and α₂C-adrenoceptor occupancy. The ED₅₀ (95% confidence limits) for α₂A-adrenoceptor occupancy was 0.014 mg/kg sc (0.009–0.019), and for α₂C-adrenoceptor occupancy was 0.026 mg/kg sc (0.022–0.030) [1] 2. Biodistribution of [¹¹C]R107474 in rats: Intravenous (iv) administration of [¹¹C]R107474 led to rapid uptake in most tissues (including the brain), with maximum concentration reached at 5 minutes post-injection (pi). The highest radioactivity uptake in the brain was observed in the septum (3.54 ± 0.52 ID/g at 5 min pi) and entorhinal cortex (1.57 ± 0.10 ID/g at 5 min pi). The tissue/cerebellum concentration ratios increased over time: 5.38 ± 0.45 for septum and 3.43 ± 0.24 for entorhinal cortex at 30 min pi, due to rapid initial uptake followed by slow washout [1] 3. In vivo blocking experiment: Co-administration of mirtazapine (a non-selective α₂-adrenoceptor antagonist) with [¹¹C]R107474 resulted in specific inhibition of [¹¹C]R107474 binding in selective brain regions [1] |
| Enzyme Assay |
1. Receptor binding assay protocol: Membrane preparations were prepared from either brain tissue or cells that stably expressed cloned human receptors (e.g., α₂-adrenoceptor subtypes, 5-HT receptors, dopamine receptors). The membrane samples were incubated with R107474 (at various concentrations) and corresponding radiolabeled ligands specific to each target receptor. After incubation, unbound radioligands were separated from membrane-bound ligands, and the radioactivity of the bound fraction was measured to determine the inhibition rate of R107474 on ligand-receptor binding. Ki values were calculated based on the inhibition curves to evaluate the affinity of R107474 for each receptor [1]
|
| Animal Protocol |
Rats: Male Wistar rats (weighing 200–250 g) are anesthetized with diethyl ether, and radiolabeled lusaperidone (24–28 GBq/μmol) is injected into their tail vein. The rats were given injections of 30–40 MBq in 300 μL saline containing 10% (v/v) ethanol at the beginning of the experiment. Under the influence of diethyl ether anesthesia, the rats are killed by cervical dislocation at 5, 10, 20, and 30 minutes after injection. After a cardiac puncture, a blood sample is obtained, and a few chosen tissues are quickly dissected and weighed. Radioactivity is quantified [1].
1. α₂-adrenoceptor occupancy assay: Animals were administered R107474 via subcutaneous injection at different doses. One hour after administration, the animals were sacrificed, and their brains were removed and processed into tissue sections. Ex vivo autoradiography was performed on the sections using appropriate radiolabeled ligands to visualize and quantify α₂A- and α₂C-adrenoceptor occupancy [1] 2. Biodistribution assay in rats: Male Wistar rats were used for the experiment. [¹¹C]R107474 was administered to rats via intravenous injection. At predetermined time points (5, 15, 30, 60 minutes post-injection), the rats were sacrificed, and various tissues (including brain regions such as septum, entorhinal cortex, cerebellum, and other peripheral tissues) were collected. The radioactivity in each tissue sample was measured, and the uptake was expressed as percentage injected dose per gram of tissue (ID/g) [1] 3. In vivo blocking experiment: Rats were pre-administered mirtazapine (a non-selective α₂-adrenoceptor antagonist) before intravenous injection of [¹¹C]R107474. After the specified time, the rats were sacrificed, and brain tissues were collected to measure the radioactivity of [¹¹C]R107474 in selective brain regions. The binding inhibition rate was calculated by comparing with rats not pre-administered mirtazapine [1] |
| ADME/Pharmacokinetics |
1. Tissue distribution: After intravenous injection of [¹¹C]R107474 in rats, the tracer was rapidly absorbed by most tissues, reaching maximum concentrations in brain and other tissues within 5 minutes post-injection. In brain tissue, the highest absorption was observed in the septum and entorhinal cortex, consistent with the known distribution of α₂-adrenergic receptors. Due to rapid absorption and slow clearance, the tissue/cerebellar concentration ratio in the septum and entorhinal cortex increased over time (within 30 minutes post-injection) [1]
|
| References | |
| Additional Infomation |
1. R107474 is a potent and relatively selective α₂-adrenergic receptor antagonist with the chemical structure 2-methyl-3-[2-(1,2,3,4-tetrahydrobenzo[4,5]furano[3,2-c]pyridin-2-yl)ethyl]-4H-pyrido[1,2-a]pyrimidin-4-one[1]
2. [¹¹C]R107474 was synthesized by Pictet-Spengler reaction with [¹¹C]formaldehyde, with a total radiochemical yield of 33 ± 4% (decay corrected), a total synthesis time of 55 minutes, and a specific activity of 24–28 GBq/μmol[1] 3. [¹¹C]R107474 is a potential positron emission tomography (PET) assay. Due to its specific binding to α₂-adrenergic receptors and its good biodistribution properties in the brain, this ligand can be used to study central α₂-adrenergic receptors [1] |
| Molecular Formula |
C₂₂H₂₁N₃O₂
|
|---|---|
| Molecular Weight |
359.42
|
| Exact Mass |
359.163
|
| Elemental Analysis |
C, 73.52; H, 5.89; N, 11.69; O, 8.90
|
| CAS # |
214548-46-6
|
| PubChem CID |
3045401
|
| Appearance |
White to light yellow solid powder
|
| Density |
1.31g/cm3
|
| Boiling Point |
538.3ºC at 760 mmHg
|
| Flash Point |
279.4ºC
|
| Vapour Pressure |
1.17E-11mmHg at 25°C
|
| Index of Refraction |
1.688
|
| LogP |
3.287
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
27
|
| Complexity |
751
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C1C(CCN2CCC(OC3=CC=CC=C34)=C4C2)=C(C)N=C5N1C=CC=C5
|
| InChi Key |
ZYXHQIPQIKTEDI-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H21N3O2/c1-15-16(22(26)25-11-5-4-8-21(25)23-15)9-12-24-13-10-20-18(14-24)17-6-2-3-7-19(17)27-20/h2-8,11H,9-10,12-14H2,1H3
|
| Chemical Name |
3-[2-(3,4-dihydro-1H-[1]benzofuro[3,2-c]pyridin-2-yl)ethyl]-2-methylpyrido[1,2-a]pyrimidin-4-one
|
| Synonyms |
R107474; R-107474; R 107474
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: ~3.45 mg/mL (~9.6 mM)
|
|---|---|
| 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 | 2.7823 mL | 13.9113 mL | 27.8226 mL | |
| 5 mM | 0.5565 mL | 2.7823 mL | 5.5645 mL | |
| 10 mM | 0.2782 mL | 1.3911 mL | 2.7823 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
