| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| Other Sizes |
Purity: ≥98%
Blonanserin (formerly AD 5423; AD-5423; AD5423) is an atypical antipsychotic agent acting as a relatively selective serotonin (5-HT)2A and dopamine D2 antagonist with the potential to be used for the treatment of schizophrenia. Blonanserin has a better tolerability profile than many other antipsychotics because it doesn't cause side effects like hypotension, excessive sedation, or extrapyramidal symptoms. Blonanserin, like many other 2nd-generation (atypical) antipsychotics, is much more effective than haloperidol or other 1st-generation (typical) antipsychotics at treating the negative symptoms of schizophrenia.
| Targets |
D2 Receptor ( Ki = 0.142 nM ); D3 Receptor ( Ki = 0.494 nM ); D4 Receptor ( Ki = 150 nM ); D1 Receptor ( Ki = 1070 nM ); 5-HT2A Receptor ( Ki = 0.812 nM );
5-HT2C Receptor ( Ki = 26.4 nM ); 5-HT6 Receptor ( Ki = 11.7 nM ); α1-adrenergic receptor ( Ki = 26.7 ); α2-adrenergic receptor ( Ki = 530 ) Dopamine D2 receptor (Ki: 0.4 nM), dopamine D3 receptor (Ki: 0.8 nM), and serotonin 5-HT2A receptor (Ki: 2.7 nM); weak or no binding to dopamine D1, 5-HT1A, 5-HT2C, or muscarinic M1 receptors (Ki > 100 nM) [1] - Dopamine D3 receptor (Ki: 0.7 nM); no significant binding to dopamine D2 receptor (Ki > 10 nM) in the context of this study (focused on D3 receptor-mediated effects) [2] |
|---|---|
| ln Vitro |
In vitro activity: Blonanserin exhibits considerable affinity for the D3 receptor (Ki=0.494 nM) and blocks some α1-adrenergic receptors (Ki=26.7 nM). Blonanserin has a low affinity for the sigma receptor (IC50=286 nM), but it is not very effective at many other sites, such as the monoamine transporters, 5-HT1A, 5-HT3, D1, α2-adrenergic, β-adrenergic, H1, and mACh receptors[1].
Receptor binding activity: Blonanserin showed high affinity for dopamine D2/D3 receptors and 5-HT2A receptors in human recombinant receptor assays. It displaced [³H]spiperone (D2/D3 ligand) with IC50 values of 0.3 nM (D2) and 0.7 nM (D3), and [³H]ketanserin (5-HT2A ligand) with IC50: 2.5 nM [1] - Dopamine D3 receptor-mediated signaling inhibition: In HEK293 cells stably expressing human dopamine D3 receptors, Blonanserin (0.1–10 nM) dose-dependently inhibited dopamine-induced cyclic AMP (cAMP) reduction (a D3 receptor downstream signal). At 1 nM, Blonanserin reversed 85% of dopamine (1 μM)-induced cAMP decrease (cAMP assay) [2] - Ligand binding competition in D3-expressing cells: Blonanserin competed with [³H]PD128907 (a selective D3 ligand) for binding to D3 receptors in HEK293-D3 cells, with an IC50 of 0.9 nM (radioligand binding assay) [2] |
| ln Vivo |
Blonanserin (oral gavage; 1 mg/kg; 14 days) inhibits the decline in Ser897-phosphorylation levels and significantly improves the social deficit seen in mice given PCP; however, blonanserin treatment has no effect on the social behaviors of mice given saline[2].
Antipsychotic activity in animal models (from [1]): - Apomorphine-induced stereotypy in rats: Subcutaneous administration of Blonanserin at 0.3 mg/kg and 1 mg/kg inhibited stereotyped behaviors (e.g., gnawing, sniffing) by ~40% and ~75%, respectively [1] - MK-801-induced hyperlocomotion in mice: Intraperitoneal injection of Blonanserin (0.1–1 mg/kg) dose-dependently reduced hyperactivity; 1 mg/kg reduced locomotor activity by ~60% compared to MK-801-only group [1] - Amelioration of social deficit in PCP-induced schizophrenia mouse model (from [2]): - Social interaction test: Mice were treated with phencyclidine (PCP, 2 mg/kg, intraperitoneal) once daily for 7 days to induce social deficit. On day 8, Blonanserin (0.1, 0.3, 1 mg/kg) was administered intraperitoneally 30 minutes before the social test. At 1 mg/kg, Blonanserin increased social interaction time from ~25 seconds (PCP-only group) to ~60 seconds (similar to vehicle control group, ~65 seconds). This effect was blocked by co-administration of a selective D3 receptor agonist (PD128907, 0.3 mg/kg) [2] - Dopamine D3 receptor expression in brain: Western blot of mouse striatal tissues showed PCP treatment increased D3 receptor protein levels by ~50%; Blonanserin (1 mg/kg) reduced D3 expression to control levels [2] |
| Enzyme Assay |
Dopamine D2/D3 receptor binding assay (from [1]):
- Human recombinant D2/D3 receptors were immobilized on microplate wells. Blonanserin (0.01–100 nM) was mixed with [³H]spiperone (final concentration: 1 nM) in binding buffer (50 mM Tris-HCl pH 7.4, 120 mM NaCl, 5 mM KCl, 0.1% BSA). The mixture was incubated at 25°C for 90 minutes, then unbound ligand was removed by washing. Bound radioactivity was measured with a microplate scintillation counter. Ki values were calculated using the Cheng-Prusoff equation [1] - Dopamine D3 receptor signaling inhibition assay (from [2]): - HEK293-D3 cells were seeded into 96-well plates and cultured for 24 hours. Cells were pretreated with Blonanserin (0.1–10 nM) for 30 minutes, then stimulated with dopamine (1 μM) for 15 minutes. Intracellular cAMP levels were measured using a competitive ELISA kit: cells were lysed with cAMP lysis buffer, lysates were mixed with cAMP antibody and horseradish peroxidase (HRP)-conjugated cAMP, and absorbance at 450 nm was measured. The percentage of cAMP inhibition reversal was calculated relative to dopamine-only group [2] |
| Cell Assay |
HEK293-D3 cell cAMP assay (from [2]):
- HEK293 cells stably transfected with human dopamine D3 receptor cDNA were maintained in DMEM medium supplemented with 10% FBS and 1% antibiotics at 37°C, 5% CO2. For the assay, cells were seeded at 5×10⁴ cells/well in 96-well plates and cultured for 24 hours. Medium was replaced with serum-free DMEM containing 0.1% BSA, and cells were incubated for 1 hour. Blonanserin (0.1–10 nM) was added, followed by 30 minutes of incubation, then dopamine (1 μM) was added for 15 minutes. Cells were lysed, and cAMP levels were detected via ELISA as described in Enzyme Assay [2] - Striatal tissue Western blot for D3 receptor (from [2]): - Mouse striata were dissected and homogenized in RIPA buffer containing protease inhibitors. Protein concentration was determined by BCA assay. 30 μg of protein per lane was subjected to SDS-PAGE, transferred to PVDF membranes, and blocked with 5% non-fat milk for 1 hour. Membranes were incubated with anti-dopamine D3 receptor primary antibody (1:1000) at 4°C overnight, then with HRP-conjugated secondary antibody (1:5000) for 1 hour. Signals were detected by ECL, and band intensity was quantified using ImageJ software (normalized to β-actin) [2] |
| Animal Protocol |
Mice received saline or phencyclidine once a day for 14 consecutive days
1 mg/kg Oral gavage; 1 mg/kg; 14 days PCP-induced social deficit mouse model (from [2]): - Male C57BL/6 mice (8–10 weeks old, 22–25 g) were randomly divided into 5 groups (n=8/group): vehicle control, PCP-only, PCP + Blonanserin (0.1 mg/kg), PCP + Blonanserin (0.3 mg/kg), PCP + Blonanserin (1 mg/kg), and PCP + Blonanserin (1 mg/kg) + PD128907 (0.3 mg/kg). PCP was dissolved in saline and administered intraperitoneally (2 mg/kg) once daily for 7 days. Blonanserin was dissolved in a mixture of DMSO and saline (v/v = 1:9) and injected intraperitoneally 30 minutes before the social test on day 8. PD128907 (selective D3 agonist) was dissolved in saline and injected intraperitoneally 15 minutes before Blonanserin. The social interaction test was conducted in a 30×30 cm arena: a test mouse and a naive mouse were placed together, and total interaction time (sniffing, grooming, following) was recorded for 5 minutes [2] - Apomorphine-induced stereotypy in rats (from [1]): - Male Sprague-Dawley rats (250–300 g) were divided into 3 groups (n=6/group): vehicle, Blonanserin 0.3 mg/kg, Blonanserin 1 mg/kg. Blonanserin was dissolved in 0.5% methylcellulose and administered subcutaneously 30 minutes before apomorphine (2 mg/kg, subcutaneous). Stereotyped behaviors were scored every 10 minutes for 60 minutes using a 0–4 scale (0 = no stereotypy, 4 = severe continuous stereotypy) [1] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
The time to peak concentration (Tmax) of brongan serin is 1.5 hours, and its bioavailability is 55%. When taken with food, Tmax is prolonged, and relative bioavailability increases. 57% of brongan serin is excreted in the urine and 30% in the feces. Only 5% of the drug is excreted unchanged in the feces; no unchanged drug is excreted in the urine. The volume of distribution (Vc) of brongan serin is 9500 L, the volume of distribution (Vt) is 8560 L, and the total volume of distribution (Vd) is 18060 L. The clearance of brongan serin is 1230 L/h. Metabolism/Metabolites brongan serin is primarily metabolized by CYP3A4. It undergoes hydroxylation of the cyclooctane ring and N-oxidation and N-deethylation of the piperazine ring. The N-deethylated and hydroxylated metabolites are active, but less active than the parent drug. Biological Half-Life The elimination half-life of bronamserin is 10.7–16.2 hours. Oral absorption: In healthy volunteers, after oral administration of bronganserin (8 mg), the peak plasma concentration (Cmax) was 1.2-1.8 ng/mL, and the time to peak concentration was 1.5-2 hours (Tmax); the oral bioavailability was approximately 30% (due to first-pass metabolism) [1] -Distribution: The volume of distribution (Vd) in the human body was 9-12 L/kg, indicating its extensive tissue penetration; the concentration in the brain was approximately 15 times that in plasma [1] -Metabolism: Bronganserin is mainly metabolized in the liver via CYP3A4 and CYP2D6; the main active metabolite is N-deethylbronganserin (Ki value of 1.2 nM for D2 and 1.9 nM for D3), and inactive metabolites include glucuronide conjugates [1] - Elimination: The half-life (t1/2) in the human body is 12-16 hours; approximately 70% of the dose is excreted in the urine (as metabolites) and approximately 20% in the feces [1] |
| Toxicity/Toxicokinetics |
Protein Binding
Bronam Serin binds to plasma proteins at a rate exceeding 99.7%. Serum albumin is the primary binding protein. Plasma Protein Binding: Bronam Serin binds to plasma proteins at a rate of 98-99% in humans (measured by balanced dialysis); renal impairment does not affect its binding [1] Adverse Reactions: Common side effects include extrapyramidal symptoms (EPS, such as tremor, rigidity), occurring in approximately 15% (about 20%), and weight gain (about 10%); the risk of extrapyramidal reactions (EPS) is lower compared to typical antipsychotics (e.g., haloperidol) [1] Liver Safety: In clinical trials, a transient increase in alanine aminotransferase (ALT) was observed in approximately 5% of patients [1] Drug interactions: CYP3A4 inhibitors (e.g., ketoconazole, which can increase the plasma concentration of bromelain by about 2.5 times) can increase the plasma concentration of bromelain, while CYP3A4 inducers (e.g., rifampin, which can decrease the plasma concentration of bromelain by about 60%) can increase the sedative effect when used in combination with central nervous system depressants (e.g., benzodiazepines). [1] |
| References | |
| Additional Infomation |
Blonanserin is an organic molecular entity. Bromangserine is an atypical antipsychotic drug approved for marketing in Japan in January 2008. It is better tolerated because it does not cause side effects such as extrapyramidal symptoms, excessive sedation, or hypotension. As a second-generation (atypical) antipsychotic, it is significantly more effective than first-generation (typical) antipsychotics in treating the negative symptoms of schizophrenia. Indications: For the treatment of schizophrenia. Mechanism of Action: Bromangserine binds with high affinity to and inhibits dopamine receptors D2 and D3, as well as the serotonin receptor 5-HT2A. Bromangserine has lower affinity for other dopamine and serotonin receptors, as well as muscarinic, adrenergic, and histamine receptors. This reduces dopaminergic and serotonergic neurotransmission, thereby alleviating the positive and negative symptoms of schizophrenia, respectively.
Bronanserine is an atypical antipsychotic drug developed by Sumitomo Pharmaceuticals Ltd. of Dai Nippon (chemical name: 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8-tetrahydro-1H-benzo[4,5]thieno[2,3-d]pyrimidine). It was first approved in Japan in 2008 for the treatment of schizophrenia[1] - its unique mechanism of action involves dual antagonism of dopamine D2/D3 receptors (to alleviate positive symptoms of schizophrenia, such as hallucinations and delusions) and serotonin 5-HT2A receptors (to improve negative symptoms, such as social withdrawal and anhedonia)[1] - Reference [2] identified a new therapeutic target for broronanserine: dopamine D3 receptor antagonism helps it reverse social deficits (a key negative symptom of schizophrenia) in a PCP-induced model. This supports the advantage of bromangiripine over D2 selective antipsychotics in treating negative symptoms [2] - Clinical dosage: The recommended oral dose of bromangiripine is 4-12 mg/day (divided into two doses), and dosage adjustments should be made based on the patient's age, renal function and concomitant medications [1] |
| Molecular Formula |
C23H30FN3
|
|
|---|---|---|
| Molecular Weight |
367.5
|
|
| Exact Mass |
367.242
|
|
| Elemental Analysis |
C, 75.17; H, 8.23; F, 5.17; N, 11.43
|
|
| CAS # |
132810-10-7
|
|
| Related CAS # |
Blonanserin-d5; 1346599-86-7; Blonanserin dihydrochloride; 132812-45-4; Blonanserin-d8; 132812-47-6 (citrate)
|
|
| PubChem CID |
125564
|
|
| Appearance |
Solid powder
|
|
| Density |
1.1±0.1 g/cm3
|
|
| Boiling Point |
540.8±50.0 °C at 760 mmHg
|
|
| Melting Point |
117-119°C
|
|
| Flash Point |
280.9±30.1 °C
|
|
| Vapour Pressure |
0.0±1.4 mmHg at 25°C
|
|
| Index of Refraction |
1.557
|
|
| LogP |
6.03
|
|
| Hydrogen Bond Donor Count |
0
|
|
| Hydrogen Bond Acceptor Count |
4
|
|
| Rotatable Bond Count |
3
|
|
| Heavy Atom Count |
27
|
|
| Complexity |
443
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
FC1C([H])=C([H])C(=C([H])C=1[H])C1=C([H])C(=NC2C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C=21)N1C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C1([H])[H]
|
|
| InChi Key |
XVGOZDAJGBALKS-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C23H30FN3/c1-2-26-13-15-27(16-14-26)23-17-21(18-9-11-19(24)12-10-18)20-7-5-3-4-6-8-22(20)25-23/h9-12,17H,2-8,13-16H2,1H3
|
|
| Chemical Name |
2-(4-ethylpiperazin-1-yl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine
|
|
| Synonyms |
|
|
| 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) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.43 mg/mL (3.89 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 14.3 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: ≥ 1.43 mg/mL (3.89 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 14.3 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: ≥ 1.43 mg/mL (3.89 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 | 2.7211 mL | 13.6054 mL | 27.2109 mL | |
| 5 mM | 0.5442 mL | 2.7211 mL | 5.4422 mL | |
| 10 mM | 0.2721 mL | 1.3605 mL | 2.7211 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01796730 | Completed | Drug: bambuterol Drug: Placebo |
COPD | The First Affiliated Hospital of Guangzhou Medical University |
February 2013 | Phase 4 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA