| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Imidazoline-1 receptor (I1R) and alpha2-adrenergic receptors (alpha2A, alpha2B, alpha2C). Ki values: I1R = 4.2+/-3.2 nmol/L; alpha2A = 13.0+/-4.2 nmol/L; alpha2B = 9.5+/-4.1 nmol/L; alpha2C = 15.6+/-9.8 nmol/L.
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|---|---|
| ln Vitro |
In vitro, moxonidine binds to I1 receptors and alpha2-adrenergic receptors with high affinity. Its mechanism of action involves activation of I1 receptors in the rostral ventrolateral medulla, leading to reduced sympathetic outflow and decreased peripheral vascular resistance. The compound shows selectivity for I1 receptors over alpha2 receptors, which contributes to its improved side-effect profile compared to older centrally acting antihypertensives.
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| ln Vivo |
In vivo, moxonidine is an effective antihypertensive agent that lowers blood pressure by reducing sympathetic tone. It is orally administered and well absorbed with bioavailability approaching 90%. The drug is effective in managing essential hypertension. Common adverse effects include dry mouth, headache, dizziness, fatigue, and occasional gastrointestinal disturbances.
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| Enzyme Assay |
Receptor binding assays are performed using membrane preparations from cells or tissues expressing I1 receptors (e.g., human or rat brainstem). Membranes are incubated with radiolabeled [3H]-clonidine or [3H]-idazoxan and varying concentrations of moxonidine (0.1 nM-100 microM) in binding buffer (50 mM Tris-HCl, pH 7.4, containing 0.5 mM EDTA and protease inhibitors) at 25degC for 60 minutes. Non-specific binding is determined in the presence of 10 microM unlabeled rilmenidine or clonidine. Bound and free ligand are separated by filtration through GF/B filters. Radioactivity is counted and Ki values are calculated from competitive binding curves. For alpha2-adrenergic receptor binding, similar assays are performed using [3H]-rauwolscine as the radioligand.
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| Cell Assay |
Cells expressing recombinant I1 receptors or alpha2-adrenergic receptors (e.g., CHO or HEK-293 cells) are seeded in 96-well plates. Functional activity is assessed by measuring inhibition of forskolin-stimulated cAMP accumulation (for alpha2 receptors, which are Gi-coupled) or by measuring calcium mobilization (for I1 receptors). Moxonidine is added at concentrations ranging from 0.1 nM to 100 microM and incubated for 15-30 minutes. cAMP levels are measured using ELISA or HTRF-based detection kits. EC₅0 values are calculated from dose-response curves. For selectivity profiling, the compound is tested against panels of related receptors (e.g., alpha1, beta-adrenergic, serotonin, dopamine receptors).
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| Animal Protocol |
In vivo antihypertensive efficacy is evaluated in spontaneously hypertensive rats (SHR) or other hypertensive animal models. Moxonidine is administered orally or intravenously at doses ranging from 0.1-3 mg/kg. Blood pressure and heart rate are measured using tail-cuff plethysmography or telemetry at multiple time points post-administration. Sympathetic outflow is assessed by measuring plasma catecholamine levels or by recording renal sympathetic nerve activity. For pharmacokinetic studies, blood samples are collected at various time points and plasma drug concentrations are measured by HPLC or LC-MS/MS.
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| ADME/Pharmacokinetics |
Doses typically range from 0.1-0.4 mg/kg orally in animal studies. Following oral administration, Tmax is approximately 1 hour and bioavailability approaches 90%. The drug is not subject to significant first-pass metabolism. Plasma protein binding is approximately 7.2%. Moxonidine is predominantly eliminated unchanged via the renal route. The half-life is approximately 2.5 hours, which is prolonged in renal insufficiency. Biotransformation is unimportant.
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| Toxicity/Toxicokinetics |
Common adverse effects include dry mouth, headache, dizziness, fatigue, and occasional gastrointestinal disturbances. Rebound hypertension may occur upon abrupt withdrawal. The drug is contraindicated in patients with severe bradycardia, sick sinus syndrome, or severe hepatic impairment. Moxonidine has a favorable safety profile compared to older centrally acting antihypertensives (e.g., clonidine) due to its greater I1 selectivity. Overdose may cause hypotension, bradycardia, and sedation.
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| References |
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| Additional Infomation |
Moxonidine hydrochloride is an approved antihypertensive medication (marketed as Physiotens® and other trade names). It was developed as a second-generation centrally acting antihypertensive with improved tolerability compared to clonidine. The compound's I1 receptor selectivity is responsible for its antihypertensive efficacy with reduced sedative and dry mouth side effects. Moxonidine has also been investigated for potential applications in metabolic syndrome, insulin resistance, and heart failure. The hydrochloride salt form (BE5895) is used for oral administration. Molecular formula is C₉H13Cl2N₅O with molecular weight 278.14.
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| Molecular Formula |
C₉H₁₃CL₂N₅O
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|---|---|
| Molecular Weight |
278.14
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| Exact Mass |
277.049
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| CAS # |
75536-04-8
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| Related CAS # |
Moxonidine;75438-57-2
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| PubChem CID |
11231255
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
17
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| Complexity |
275
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=NC(=C(C(=N1)Cl)NC2=NCCN2)OC.Cl
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| InChi Key |
ZZPAWQYZQVUVHX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C9H12ClN5O.ClH/c1-5-13-7(10)6(8(14-5)16-2)15-9-11-3-4-12-9;/h3-4H2,1-2H3,(H2,11,12,15);1H
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| Chemical Name |
4-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-6-methoxy-2-methylpyrimidin-5-amine;hydrochloride
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| Synonyms |
BE 5895; BDF5895 hydrochloride
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : ~100 mg/mL (~359.53 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.99 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 25.0 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: ≥ 2.5 mg/mL (8.99 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 25.0 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: ≥ 2.5 mg/mL (8.99 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 | 3.5953 mL | 17.9766 mL | 35.9531 mL | |
| 5 mM | 0.7191 mL | 3.5953 mL | 7.1906 mL | |
| 10 mM | 0.3595 mL | 1.7977 mL | 3.5953 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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