| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
Alpha 2B-adrenoceptor
Imiloxan hydrochloride targets the α2-adrenoceptor, specifically the α2B subtype. It is a moderately potent, but highly selective antagonist. It shows no affinity for α1-adrenoceptor. By blocking α2B-ARs, it modulates sympathetic nervous system processes, including smooth muscle contraction and neurotransmission. It has a Ki value of 50.12 nM for the human α2B-AR. |
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| ln Vitro |
1. The alpha 2-adrenoceptor binding sites of rabbit spleen and rat kidney, labelled with [3H]-rauwolscine, were characterized using a range of subtype selective ligands. 2. In rabbit spleen, the alpha-2-adrenoceptor binding sites displayed high affinity for oxymetazoline and WB 4101 and low affinity for prazosin and chlorpromazine suggesting the presence of an alpha 2A subtype. 3. There was evidence for heterogeneity of the alpha 2-adrenoceptor binding sites present in rabbit spleen. The results obtained with oxymetazoline and WB 4101 indicated that at least 75% of the [3H]-rauwolscine binding sites in this preparation displayed a pharmacology consistent with the presence of an alpha 2A subtype. 4. In rat kidney, the alpha 2-adrenoceptor binding sites displayed high affinity for prazosin and chlorpromazine and low affinity for oxymetazoline and WB 4101 suggesting the presence of an alpha 2B subtype. 5. The inclusion of guanylylimidodiphosphate (Gpp(NH)p, 0.1 mM) did not modify the pharmacology of the alpha 2-adrenoceptor binding sites present in the two preparations. Furthermore, when the two membrane preparations were combined, the resultant pharmacology was still consistent with the presence of two receptors that retained the characteristics of the alpha 2A and alpha 2B subtypes. 6. Imiloxan was identified as a selective alpha 2B ligand while benoxathian displayed a high degree of selectivity for the alpha 2A-adrenoceptor binding site. The selectivity of Imiloxan for the alpha 2B-adrenoceptor binding site, coupled with its specificity for alpha 2-adrenoceptors, should make it a valuable tool in the classification of alpha 2-adrenoceptor subtypes [1].
In vitro, Imiloxan hydrochloride acts as a potent and selective α2B-adrenoceptor antagonist. Its activity is typically assessed by measuring its ability to inhibit agonist-induced responses in cells or tissues expressing α2B-ARs. It shows no affinity for α1-adrenoceptor. The compound has an IC50 of 10 µM against Plasmodium falciparum. It has potential in acute kidney injury research. |
| ln Vivo |
Excitation of renal sympathetic nervous activity and the resulting increased levels of renal venous norepinephrine play important roles in renal ischaemia/reperfusion injury in rats. This study examined the effects of yohimbine, a non-selective α2-adrenoceptor antagonist, on renal venous norepinephrine levels and kidney function in acute kidney injury. Acute ischaemia/reperfusion-induced kidney injury was induced in rats by clamping the left renal artery and vein for 45min, followed by reperfusion, 2 weeks after a contralateral nephrectomy. Intravenous injection of yohimbine (0.1mg/kg) 5min prior to ischaemia significantly attenuated kidney injury and decreased the renal venous norepinephrine levels, as compared with vehicle-treated rats. To investigate the involvement of α2-adrenoceptor subtypes, we pre-treated with JP-1302, a selective α2C-adrenoceptor antagonist (1mg/kg). This suppressed renal venous norepinephrine levels and tumour necrosis factor-α and monocyte chemoattractant protein-1 mRNA levels after reperfusion and improved kidney function. Pre-treatment with BRL44408, a selective α2A-adrenoceptor antagonist (1mg/kg), or Imiloxan, a selective α2B-adrenoceptor antagonist (1mg/kg) had no effect on renal function or tissue injury. These results suggest that yohimbine prevented ischaemia/reperfusion-induced kidney injury by inhibiting α2C-adrenoceptors and suppressing pro-inflammatory cytokine expression.
In vivo, Imiloxan hydrochloride has potential in acute kidney injury research. As a highly selective α2B-AR antagonist, it would be expected to modulate sympathetic nervous system activity. However, comprehensive in vivo efficacy data from published literature are limited. The compound is primarily used as a research tool to study the physiological and pathological roles of the α2B-adrenoceptor subtype. |
| Enzyme Assay |
For non-cell-based receptor binding assays, Imiloxan hydrochloride can be evaluated using membrane preparations from cells expressing human α2B-adrenergic receptors. Radioligand binding displacement experiments are performed using a suitable radiolabeled ligand such as [3H]-RX821002. Membrane homogenates are incubated with increasing concentrations of the test compound and a fixed concentration of the radioligand. Bound radioligand is separated from free by rapid filtration through glass fiber filters. Non-specific binding is determined in the presence of excess unlabeled yohimbine. Ki values are calculated from displacement curves using nonlinear regression analysis.
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| Cell Assay |
For in vitro cellular assays, cells expressing human α2B-adrenergic receptors are cultured in appropriate media. For functional assays, the inhibition of forskolin-stimulated cAMP accumulation is measured. Cells are treated with various concentrations of Imiloxan hydrochloride in the presence of an α2-agonist. cAMP levels are measured using ELISA or HTRF-based detection. The compound's ability to reverse the agonist-induced inhibition of cAMP accumulation is assessed, and IC50 values are calculated from dose-response curves.
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| Animal Protocol |
Male Sprague-Dawley rats (8 weeks old) were housed in a light-controlled room with a 12-h light/dark cycle and ad libitum access to food and water. The right kidney was removed through a small flank incision under pentobarbital anaesthesia (50 mg/kg, intraperitoneally [i.p.]). After a 2-week recovery period, the rats were divided into six groups: (1) sham-operated control without ischaemia; (2) vehicle treatment (0.9% saline, 1 mg/kg, intravenously [i.v.]) followed by ischaemia/reperfusion; (3) yohimbine treatment (0.1 mg/kg, i.v.) followed by ischaemia/reperfusion; (4) BRL44408 treatment (1 mg/kg, i.v.) followed by ischaemia/reperfusion; (5) Imiloxan treatment (1 mg/kg, i.v.) followed by ischaemia/reperfusion; and (6) JP-1302 treatment (1 mg/kg, i.v.) followed by ischaemia/reperfusion. All drug doses were selected based on previous in vivo studies (Docherty, 1983, Young et al., 2010, Imaki et al., 2009, Galeotti et al., 2004, Myers et al., 2004) and these i.v. treatments were injected into the external jugular vein 5 min before the start of ischaemia, in a volume of 0.1 or 1 ml/kg. [2]
For in vivo animal studies, Imiloxan hydrochloride can be administered to rodents via intraperitoneal injection. In models of acute kidney injury, the compound's effects on renal function and tissue damage are assessed. In models of sympathetic nervous system modulation, its effects on blood pressure and heart rate are monitored. Dosing regimens vary depending on the specific model and desired exposure levels. Blood and tissue samples may be collected for pharmacokinetic analysis. |
| ADME/Pharmacokinetics |
Imiloxan hydrochloride has a molecular weight of 280.75 and a molecular formula of C14H16N2O2·HCl. It is soluble in water (30 mg/ml). The compound should be stored desiccated at room temperature. It has a Ki value of 50.12 nM for the human α2B-AR. It is for research use only and is not intended for diagnostic or therapeutic use.
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| Toxicity/Toxicokinetics |
The toxicity profile of Imiloxan hydrochloride has not been extensively reported. As a selective α2B-AR antagonist, potential adverse effects may include modulation of sympathetic nervous system function. The compound is for research use only and is not intended for human consumption. Standard toxicological evaluation would include acute and repeated-dose toxicity studies, as well as assessment of cardiovascular and renal function.
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| References | |
| Additional Infomation |
Since the concentration of norepinephrine in the renal vein of rats pretreated with BRL44408 or mirtaza was not measured in this experiment, it is unclear whether the release of norepinephrine is affected by α2A-adrenergic receptors or α2C-adrenergic receptors. Further research is needed to elucidate the role of norepinephrine in regulating tumor necrosis factor-α and other pro-inflammatory cytokines through α2-adrenergic receptors in renal ischemia/reperfusion injury. In summary, we demonstrate that pre-ischemic treatment with yohimbine and JP-1302 can prevent ischemia/reperfusion-induced renal injury by inhibiting renal venous plasma norepinephrine levels and the expression of tumor necrosis factor-α and monocyte chemoattractant protein-1, thereby affecting α2C-adrenergic receptors (Figure 10). Our study may contribute to the development of new therapeutic strategies to alleviate renal dysfunction in acute kidney injury caused by ischemia/reperfusion. [2]
Imiloxan hydrochloride (RS 21361) is a moderately potent and highly selective α2-adrenoceptor antagonist. It is a highly selective α2B-AR antagonist. It shows no affinity for α1-adrenoceptor. Imiloxan hydrochloride has potential in acute kidney injury research. It has a Ki value of 50.12 nM for the human α2B-AR. It is available for research purposes only. |
| Molecular Formula |
C14H17CLN2O2
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| Molecular Weight |
280.75
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| Exact Mass |
280.098
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| Elemental Analysis |
C, 59.89; H, 6.10; Cl, 12.63; N, 9.98; O, 11.40
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| CAS # |
81167-22-8
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| Related CAS # |
Imiloxan;81167-16-0; 86710-23-8 (HCl); 81167-22-8 (HCl)
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| PubChem CID |
172975
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| Appearance |
White to light yellow solid powder
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| LogP |
3.087
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
19
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| Complexity |
275
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.CCN1C=CN=C1C[C@@H]1COC2=CC=CC=C2O1
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| InChi Key |
ANDJPJNFVJXEKX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H16N2O2.ClH/c1-2-16-8-7-15-14(16)9-11-10-17-12-5-3-4-6-13(12)18-11;/h3-8,11H,2,9-10H2,1H3;1H
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| Chemical Name |
2-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)-1-ethylimidazole;hydrochloride
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| Synonyms |
Imiloxan hydrochloride; Imiloxan HCl; 81167-22-8; 86710-23-8; Imiloxan hydrochloride [USAN]; UNII-X72FO6ZLZY; X72FO6ZLZY; RS 21361;
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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) |
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
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| 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 | 3.5619 mL | 17.8094 mL | 35.6189 mL | |
| 5 mM | 0.7124 mL | 3.5619 mL | 7.1238 mL | |
| 10 mM | 0.3562 mL | 1.7809 mL | 3.5619 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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