Guanoxabenz (Hydroxyguanabenz) HCl is an α2 adrenergic receptor agonist/activator with a Ki of 4000 nM and a Ki of α2A of 40 nM.

Physicochemical Properties

Molecular Formula	C8H9CL3N4O
Molecular Weight	283.54
Exact Mass	281.984
CAS #	23256-40-8
Related CAS #	Guanoxabenz;24047-25-4
PubChem CID	9567830
Appearance	Off-white to gray solid powder
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	3
Heavy Atom Count	16
Complexity	249
Defined Atom Stereocenter Count	0
SMILES	Cl.ON/C(=N/N=C/C1C(Cl)=CC=CC=1Cl)/N
InChi Key	PQPZROSFRCBPIM-AQCBZIOHSA-N
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+;
Chemical Name	2-[(E)-(2,6-dichlorophenyl)methylideneamino]-1-hydroxyguanidine;hydrochloride
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 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)

Biological Activity

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].
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].
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.
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.

Solubility Data

Solubility (In Vitro)

DMSO: 83.33 mg/mL (293.89 mM)

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. 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. 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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

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.