| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
5-HT1A Receptor 0.19 nM (Ki, In calf hippocampus) 5-HT1A Receptor 0.25 nM (Ki, In rat and human cortex) 5-HT1A Receptor 0.59 nM (Ki, In rat hippocampus) 5-HT7 Receptor 6 nM (Ki)
Repinotan targets the serotonin 5-HT1A receptor with high affinity and selectivity. It is a potent and selective agonist at this receptor, with Ki values ranging from 0.19 to 0.59 nM depending on the tissue source. The compound shows weaker affinity for other related receptors. By activating 5-HT1A receptors, Repinotan modulates serotonergic neurotransmission, which is involved in mood regulation, anxiety, and neuroprotection. |
|---|---|
| ln Vitro |
5-HT7 (Ki = 6 nM), α1- and α2 adrenergic (Ki = 6 nM and 7 nM, respectively), 5-HT1D (36 nM), dopamine D2 and D4 (48 nM and 91 nM, respectively), σ sites (176 nM), and 5-HT2C (310 nM) receptors are among those to which repinotan binds with a lesser affinity[1]. Rat cortical and hippocampus neurons in vitro are shielded against apoptosis caused by 25 nM staurosporine by exposure to repinotan. Repinotan inhibits the release of lactate dehydrogenase, DNA fragmentation, and poptotic body formation following staurosporine-induced apoptosis in a concentration-dependent manner, ranging from 50 pM to 1 μM[1].
In vitro, Repinotan acts as a potent 5-HT1A receptor agonist. Its activity is typically assessed by measuring its ability to stimulate [35S]GTPγS binding or inhibit forskolin-stimulated cAMP accumulation in cells expressing 5-HT1A receptors. The compound inhibits glutamate-induced depolarization in neuronal cells. Its high affinity (Ki = 0.19-0.59 nM) and selectivity for 5-HT1A over other receptors make it a valuable tool for studying 5-HT1A receptor function and signaling pathways. |
| ln Vivo |
In the paradigms of permanent middle cerebral artery blockage, temporary middle cerebral artery occlusion, and traumatic brain injury, repinotan (1–100 μg/kg) significantly reduces infarcts in a dose-dependent manner[1]. Repinotan has a brief half-life in plasma (t1/2 = 0.6 h in rats and 0.4 h in rhesus monkeys), and it undergoes significant metabolism[1].
In vivo, Repinotan has been shown to reduce cortical infarct volume in pre-clinical models of stroke and brain injury, even when administered up to 5 hours after injury. As a brain-penetrant and orally active compound, it is suitable for systemic administration in animal models. Early clinical trials demonstrated that the drug was safe, with primarily serotonergic side effects such as nausea and vomiting. The compound has been investigated for its neuroprotective potential in acute neurological conditions. |
| Enzyme Assay |
For non-cell-based receptor binding assays, Repinotan can be evaluated using membrane preparations from tissues expressing 5-HT1A receptors, such as calf hippocampus, rat cortex, or human cortex. Radioligand binding displacement experiments are performed using a suitable radiolabeled ligand such as [3H]-8-OH-DPAT. Membrane homogenates are incubated with increasing concentrations of the test compound and a fixed concentration of the radioligand at room temperature for 60-90 minutes. Bound radioligand is separated from free by rapid filtration through glass fiber filters. Non-specific binding is determined in the presence of excess unlabeled 8-OH-DPAT. Ki values are calculated from displacement curves using nonlinear regression analysis.
|
| Cell Assay |
For in vitro cellular assays, cells expressing human 5-HT1A receptors (e.g., CHO or HEK293 cells) are cultured in appropriate media. For functional activity, the inhibition of forskolin-stimulated cAMP accumulation is measured. Cells are treated with various concentrations of Repinotan, and cAMP levels are measured using ELISA or HTRF-based detection. The EC50 for cAMP inhibition is calculated from dose-response curves. For [35S]GTPγS binding assays, membrane preparations are incubated with GDP, [35S]GTPγS, and various concentrations of the compound, and bound [35S]GTPγS is measured by filtration.
|
| Animal Protocol |
For in vivo animal studies, Repinotan can be administered to rodents via oral gavage or intraperitoneal injection. In models of focal cerebral ischemia, the compound's ability to reduce infarct volume is assessed following administration. In models of brain injury, neurological scores and tissue damage are evaluated. In behavioral models, the compound's effects on anxiety, depression, and cognitive function are assessed. Dosing regimens vary depending on the specific model and desired exposure levels. Blood and tissue samples may be collected for pharmacokinetic analysis.
|
| ADME/Pharmacokinetics |
Repinotan is an orally active, brain-penetrant compound with a molecular weight of 324.42 and a molecular formula of C20H24N2O2. It is soluble in DMSO and can be formulated for both in vitro and in vivo administration. The compound should be stored at -20°C for long-term stability. Its pharmacokinetic profile includes good oral bioavailability and blood-brain barrier penetration, making it suitable for central nervous system research applications.
|
| Toxicity/Toxicokinetics |
The toxicity profile of Repinotan has been evaluated in early clinical trials, which showed that the drug was safe with primarily serotonergic side effects such as nausea and vomiting. As a 5-HT1A receptor agonist, potential adverse effects may include those associated with serotonergic modulation, including gastrointestinal disturbances, dizziness, and headache. The compound is for research use only and is not intended for human consumption outside of approved clinical trials. Standard toxicological evaluation would include acute and repeated-dose toxicity studies.
|
| References |
[1]. A C Berends, et al. A review of the neuroprotective properties of the 5-HT1A receptor agonist repinotan HCl (BAYx3702) in ischemic stroke. CNS Drug Rev. Winter 2005;11(4):379-402.
|
| Additional Infomation |
Repinotane is a high-affinity, selective, full agonist of the 5-HT1A receptor subtype with neuroprotective effects.
Drug Indications It has been studied for the treatment of stroke, cerebral ischemia, and depression. Mechanism of Action Repinotane is a 5-HT1A receptor agonist that inhibits glutamate-induced depolarization. It has been reported that repinotane's effects on neurons are mediated through multiple mechanisms/signaling pathways, including activation of the anti-apoptotic phosphatidylinositol 3-kinase (PI-3K) pathway, inhibition of glutamate release (possibly through opening K+ channels leading to membrane hyperpolarization), stimulation of Bcl-2 expression by extracellular regulated kinase (Erk) or inhibition of caspase-3 activity, and increased release of neurite extension factor S-100β. Repinotan (BAY x 3702 free base, CAS 144980-29-0) is a potent, selective, brain-penetrant and orally active 5-HT1A receptor agonist. It demonstrates Ki values of 0.19 nM (calf hippocampus), 0.25 nM (rat and human cortex), and 0.59 nM (rat hippocampus). The compound has been investigated for its neuroprotective effects in pre-clinical models of stroke and brain injury, showing reduced cortical infarct volume. Early clinical trials demonstrated safety with primarily serotonergic side effects. It is available for research purposes only. |
| Molecular Formula |
C21H24N2O4S
|
|---|---|
| Molecular Weight |
400.49
|
| Exact Mass |
400.146
|
| CAS # |
144980-29-0
|
| Related CAS # |
Repinotan hydrochloride;144980-77-8
|
| PubChem CID |
198757
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.284g/cm3
|
| Boiling Point |
599.5ºC at 760 mmHg
|
| Flash Point |
316.4ºC
|
| Vapour Pressure |
2.49E-14mmHg at 25°C
|
| Index of Refraction |
1.603
|
| LogP |
4.004
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
28
|
| Complexity |
647
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C1=CC=C2C(=C1)CC[C@H](CNCCCCN3C(=O)C4=CC=CC=C4S3(=O)=O)O2
|
| InChi Key |
YGYBFMRFXNDIPO-QGZVFWFLSA-N
|
| InChi Code |
InChI=1S/C21H24N2O4S/c24-21-18-8-2-4-10-20(18)28(25,26)23(21)14-6-5-13-22-15-17-12-11-16-7-1-3-9-19(16)27-17/h1-4,7-10,17,22H,5-6,11-15H2/t17-/m1/s1
|
| Chemical Name |
2-[4-[[(2R)-3,4-dihydro-2H-chromen-2-yl]methylamino]butyl]-1,1-dioxo-1,2-benzothiazol-3-one
|
| Synonyms |
Repinotan; BAY-3702; 144980-29-0; 05PB82Z52L; DTXSID80162857; repinotanum; BAY x 3702
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 2.4969 mL | 12.4847 mL | 24.9694 mL | |
| 5 mM | 0.4994 mL | 2.4969 mL | 4.9939 mL | |
| 10 mM | 0.2497 mL | 1.2485 mL | 2.4969 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
