Apraclonidine (ALO 2145) dihydrochloride is a selective α2 and weak α1 receptor agonist that effectively reduces intraocular pressure. Apraclonidine dihydrochloride is also available as a topical eye drop.

Physicochemical Properties

Molecular Formula	C9H10N4CL2.2[HCL]
Molecular Weight	318.03
Exact Mass	315.982
CAS #	73217-88-6
Related CAS #	Apraclonidine;66711-21-5; 73218-79-8 (HCl)
PubChem CID	21479682
Appearance	Typically exists as solid at room temperature
LogP	3.969
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	2
Heavy Atom Count	17
Complexity	247
Defined Atom Stereocenter Count	0
InChi Key	XLKICJXKWJUSPK-UHFFFAOYSA-N
InChi Code	InChI=1S/C9H10Cl2N4.2ClH/c10-6-3-5(12)4-7(11)8(6)15-9-13-1-2-14-9;;/h3-4H,1-2,12H2,(H2,13,14,15);2*1H
Chemical Name	2,6-dichloro-1-N-(4,5-dihydro-1H-imidazol-2-yl)benzene-1,4-diamine;dihydrochloride
Synonyms	Apraclonidine dihydrochloride; 73217-88-6; p-Aminoclonidine dihydrochloride; Apraclonidine dihydrochloride [MI]; UNII-5AVH7Z1L0J; 5AVH7Z1L0J; p-aminoclonidine; 2,6-dichloro-1-N-(4,5-dihydro-1H-imidazol-2-yl)benzene-1,4-diamine;dihydrochloride;
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)

Biological Activity

Targets	α2/α1 receptor
ln Vitro	Because it has less negative systemic effects and less penetration into the cornea and blood-brain barrier, apaclonidine hydrochloride (ALO 2145) is more frequently used topically to treat glaucoma [2].
ln Vivo	The apraclonidine (1.15%, single infusion) inhibits 98% of PGE2-induced increases in aqueous humor flare [3]. Apraclonidine hydrochloride (ALO 2145) is effective in human glaucoma and animal models of elevated intraocular pressure. The IOP-lowering effect of apraclonidine is generally attributed to reduced aqueous humor synthesis and vasoconstriction of the anterior branches of the ophthalmic artery [2]. A single instillation of apraclonidine 1.15%, two instillations of epinephrine 1.25%, two instillations of dipivefrin 0.1%, and two instillations and one instillation of dipivefrin 0.04% eye drops inhibited 98%, 96%, 87%, 73%, and 47% of PGE(2)-induced aqueous flare elevation, respectively. Timolol 0.5%, nipradilol 0.25%, dorzolamide 1%, and pilocarpine 2% eye drops had no effects on the increase of PGE(2)-induced flare. Conclusions: Apraclonidine, epinephrine, and dipivefrin eye drops inhibit PGE(2)-induced elevation of aqueous flare in pigmented rabbits [3].
Animal Protocol	Animal/Disease Models: Male rabbit [3]. Doses: 1.15% Route of Administration: Apraclonidine (1.15%, single infusion) Experimental Results: Inhibited PGE2-induced increase in aqueous humor flare in pigmented rabbits.
ADME/Pharmacokinetics	Absorption, Distribution and Excretion Topical use of apraclonidine ophthalmic solution leads to systemic absorption. Studies of apraclonidine (0.5% ophthalmic solution) dosed one drop three times a day in both eyes for 10 days in normal volunteers yielded mean peak and trough concentrations of 0.9 ng/mL and 0.5 ng/mL, respectively. Biological Half-Life 8 hours
Toxicity/Toxicokinetics	Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the use of apraclonidine during breastfeeding. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue. One manufacturer recommends avoiding breastfeeding on the one day on which it is used for argon laser trabeculoplasty, argon laser iridotomy or posterior capsulotomy. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding 98.7% rat LD50 oral 38 mg/kg Medicamentos de Actualidad., 24(557), 1988 rat LD50 intravenous 9 mg/kg Medicamentos de Actualidad., 24(557), 1988 mouse LD50 oral 3 mg/kg Medicamentos de Actualidad., 24(557), 1988 mouse LD50 intravenous 6 mg/kg Medicamentos de Actualidad., 24(557), 1988
References	[1]. Apraclonidine in the treatment of ptosis. J Neurol Sci. 2017;376:129‐132. [2]. Aqueous humor dynamics in anesthetized rats infused with intracameral apraclonidine. Pharmacology. 1999;58(4):220‐226. [3]. Effects of topical antiglaucoma eye drops on prostaglandin E(2)-induced aqueous flare elevation in pigmented rabbits. Invest Ophthalmol Vis Sci. 2002 Apr;43(4):1142-5.
Additional Infomation	Apraclonidine is an imidazoline that is 2-amino 4,5-dihydro-1H-imidazoline in which one of the exocyclic amino hydrogens has been replaced by a 4-amino-2,6-dichlorophenyl group. It has a role as an alpha-adrenergic agonist, an antiglaucoma drug, an ophthalmology drug, a beta-adrenergic agonist and a diagnostic agent. It is a member of imidazolines, a dichlorobenzene and a member of guanidines. It is a conjugate base of an apraclonidine(1+). Apraclonidine, also known as iopidine, is a sympathomimetic used in glaucoma therapy. It is an alpha2-adrenergic agonist. Apraclonidine is an alpha-Adrenergic Agonist. The mechanism of action of apraclonidine is as an Adrenergic alpha-Agonist. Apraclonidine is a clonidine derivative with selective alpha-2-adrenergic agonistic activity. Upon ocular administration, apraclonidine enhances aqueous humor uveoscleral outflow and decreases aqueous production by vasoconstriction. This may decrease intraocular pressure (IOP). See also: Apraclonidine Hydrochloride (has salt form). Drug Indication For prevention or reduction of intraoperative and postoperative increases in intraocular pressure (IOP) before and after ocular laser surgery when used prophylactically. Also used as a short-term adjunctive therapy in patients with open-angle glaucoma who are on maximally tolerated medical therapy requiring additional IOP reduction. FDA Label Mechanism of Action Apraclonidine is a relatively selective alpha2 adrenergic receptor agonist that stimulates alpha1 receptors to a lesser extent. It has a peak ocular hypotensive effect occurring at two hours post-dosing. The exact mechanism of action is unknown, but fluorophotometric studies in animals and humans suggest that Apraclonidine has a dual mechanism of action by reducing aqueous humor production through the constriction of afferent ciliary process vessels, and increasing uveoscleral outflow.

Solubility Data

Solubility (In Vitro)

Typically soluble in DMSO (e.g. 10 mM)

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.1444 mL	15.7218 mL	31.4436 mL
	5 mM	0.6289 mL	3.1444 mL	6.2887 mL
	10 mM	0.3144 mL	1.5722 mL	3.1444 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.