| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
alpha2-adrenergic receptor (agonist, Ki=4000 nM); alpha2A adrenoceptor (fully activated form Ki=40 nM)
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|---|---|
| ln Vitro |
A number of N-hydroxyguanidine analogs of Guanoxabenz as well as a number of metabolic inhibitors, such as allopurinol, 1-chloro-2,4-dinitrobenzene, 5,59-dithiobis-(2-nitrobenzoic acid), cibacron blue, phenyl-p-benzoquinone, didox, and trimidox, appear to inhibit the formation of high-affinity Guanoxabenz binding. Preincubating the membranes with the Guanoxabenz analogue LW03 N-hydroxyguanidine inhibits the production of Guanoxabenz high-affinity binding in a manner that is dependent on both time and concentration[1]. Guanoxabenz is reduced to guanabenz by the cytosolic portion of the spleen, and guanabenz has an almost 100-fold greater affinity for rat alpha2A-adrenoceptors than does guanoxabenz[2].
Guanoxabenz shows increased binding affinity in rat brain membranes when NADH or NADPH cofactors are added, suggesting the presence of an enzyme in the rat cerebral cortex that activates Guanoxabenz, creating a metabolite with high affinity for alpha2-adrenoceptors. The fully activated form has a Ki of 40 nM for the alpha2A adrenoceptor. |
| ln Vivo |
The names "guanoxabenz" and "guanabenz" refer to centrally acting antihypertensive medications. Rat brain membranes exhibit high affinity Guanoxabenz binding upon the presence of NADPH or NADH cofactors. A metabolite with a strong affinity for alpha 2-adrenoceptors can be formed by activating Guanoxabenz through an enzymatic activity seen in the cerebral cortex of rats[3]. A dose of 1 mg/kg is chosen because it creates a noticeable and long-lasting behavioral hypoactivity. Guanoxabenz (0.1-3 mg/kg, ip) causes a dose-related reduction in locomotor activity[4].
Cellular activity data show that Guanoxabenz hydrochloride is an alpha2 adrenergic receptor agonist. High affinity Guanoxabenz binding is induced in rat brain membranes after addition of NADH or NADPH cofactors, indicating enzymatic reduction to an active metabolite. This activation mechanism distinguishes it from other alpha2 agonists. |
| Enzyme Assay |
Radioligand binding assays for alpha2-adrenergic receptors are performed using membrane preparations from rat brain cortex. [3H]-RX821002 or [3H]-rauwolscine is used as the radioligand. NADH or NADPH cofactors (1 mM) are added to the incubation mixture to activate Guanoxabenz. Test compound is incubated with membranes at varying concentrations for 30-60 min at 25degC. Bound radioligand is separated by filtration and counted by scintillation. Ki values are calculated from competition curves.
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| Cell Assay |
Cell-based functional assays for alpha2-adrenergic agonism use CHO or HEK-293 cells expressing human alpha2A receptors. Cells are treated with serial dilutions of Guanoxabenz hydrochloride in the presence of NADH or NADPH (for activation). Agonist activity is measured by quantifying inhibition of forskolin-stimulated cAMP accumulation via HTRF or ELISA. EC50 is calculated from concentration-response curves.
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| Animal Protocol |
Animal/Disease Models: Rats[4].
Doses: 0.5 mg/kg (RX 781094 or saline vehicle was injected intravenously (iv) (tail vein) at the time of peak effect of the agonist (20min for clonidine and 30 min for Guanoxabenz). Route of Administration: IP. Experimental Results: RX 781094 (0.1-1.0 mg/kg, iv) produces a rapid (< 5 set) and complete antagonism of the EEG and behavioral effects induced by clonidine and Guanoxabenz. In vivo animal studies for Guanoxabenz typically involve oral or intravenous administration to spontaneously hypertensive rats (SHR). Blood pressure is measured via tail-cuff plethysmography or telemetry at multiple time points after dosing. The compound demonstrates centrally acting antihypertensive effects mediated through alpha2-adrenergic receptor activation in the brainstem. |
| ADME/Pharmacokinetics |
Guanoxabenz is a centrally acting antihypertensive agent that requires metabolic activation to its fully active form. The active metabolite shows high affinity for alpha2A adrenoceptors (Ki=40 nM). The compound is orally bioavailable and produces blood pressure-lowering effects through central sympathetic outflow reduction.
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| Toxicity/Toxicokinetics |
Toxicity data for Guanoxabenz are limited as it is a research compound. Standard preclinical safety assessment would include acute and repeat-dose toxicity studies in rodents. Potential side effects associated with alpha2 agonists include sedation, dry mouth, bradycardia, and rebound hypertension upon withdrawal.
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| References |
[1]. Uhlén S, et al. Characterization of the enzymatic activity for biphasic competition by guanoxabenz (1-(2,6-dichlorobenzylidene-amino)-3-hydroxyguanidine) at alpha2-adrenoceptors. I. Description of an enzymatic activity in spleen membranes. Biochem Pharmac
[2]. Dambrova M, et al. Characterization of the enzymatic activity for biphasic competition by guanoxabenz (1-(2,6-dichlorobenzylidene-amino)-3-hydroxyguanidine) at alpha2-adrenoceptors. II. Description of a xanthine-dependent enzymatic activity in spleen cyto [3]. Dambrova M, et al. Characterization of Guanoxabenz reducing activity in rat brain. Pharmacol Toxicol. 1998 Oct;83(4):158-63. [4]. P W Dettmar, et al. Neuropharmacological studies in rodents on the action of RX 781094, a new selective alpha 2-adrenoceptor antagonist. Neuropharmacology. 1983 Jun;22(6):729-37. |
| Additional Infomation |
Guanoxabenz (Hydroxyguanabenz) hydrochloride is a research compound primarily used to study alpha2-adrenergic receptor function and its role in cardiovascular regulation. It is a prodrug that requires enzymatic reduction to the fully active form with high alpha2A affinity (Ki=40 nM). As of current information, Guanoxabenz has not received regulatory approval for clinical use and remains in the research stage for potential applications in neurodegenerative diseases and metabolic disorders.
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| Molecular Formula |
C8H9CL3N4O
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|---|---|
| Molecular Weight |
283.54
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| Exact Mass |
281.984
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| CAS # |
23256-40-8
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| Related CAS # |
Guanoxabenz;24047-25-4
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| PubChem CID |
9567830
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| Appearance |
Off-white to gray solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
16
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| Complexity |
249
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.ON/C(=N/N=C/C1C(Cl)=CC=CC=1Cl)/N
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| InChi Key |
PQPZROSFRCBPIM-AQCBZIOHSA-N
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| InChi Code |
InChI=1S/C8H8Cl2N4O.ClH/c9-6-2-1-3-7(10)5(6)4-12-13-8(11)14-15;/h1-4,15H,(H3,11,13,14);1H/b12-4+;
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| Chemical Name |
2-[(E)-(2,6-dichlorophenyl)methylideneamino]-1-hydroxyguanidine;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, avoid exposure to moisture. |
| 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: 83.33 mg/mL (293.89 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.34 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 20.8 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: ≥ 2.08 mg/mL (7.34 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 20.8 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: ≥ 2.08 mg/mL (7.34 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 | 3.5268 mL | 17.6342 mL | 35.2684 mL | |
| 5 mM | 0.7054 mL | 3.5268 mL | 7.0537 mL | |
| 10 mM | 0.3527 mL | 1.7634 mL | 3.5268 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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