α2/α1 receptor

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].

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].

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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/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.

Absorption, Distribution and Excretion
Topical application of apraclone eye drops can lead to systemic absorption. Studies in healthy volunteers showed that, with one drop of apraclone (0.5% eye drops) three times daily for 10 consecutive days in both eyes, the average peak and trough concentrations were 0.9 ng/mL and 0.5 ng/mL, respectively. Biological Half-Life 8 hours

Effects During Pregnancy and Lactation
◉ Summary of Use During Lactation
There is currently no information regarding the use of apraclofen during lactation. To significantly reduce the amount of medication that enters breast milk after using eye drops, press your finger against the tear duct near the corner of your eye for at least 1 minute, then wipe away any excess medication with absorbent tissue. One manufacturer recommends avoiding breastfeeding on the day of argon laser trabeculoplasty, argon laser iridotomy, or posterior capsulotomy.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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Protein binding
98.7%

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Oral LD50 in rats: 38 mg/kg, Medicamentos de Actualidad., 24(557), 1988
Intravenous LD50 in rats: 9 mg/kg, Medicamentos de Actualidad., 24(557), 1988
Oral LD50 in mice: 3 mg/kg, Medicamentos de Actualidad., 24(557), 1988
Intravenous LD50 in mice: 6 mg/kg, Medicamentos de Actualidad., 24(557), 1988

[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.

Apraclodin hydrochloride is the hydrochloride salt of apraclodin. It is an alpha-adrenergic agonist and antiglaucoma drug. It contains apraclodin. Apraclodin hydrochloride is the hydrochloride form of apraclodin, a clonidine derivative with selective alpha-2-adrenergic agonist activity. When instilled directly into the eye, apraclodin hydrochloride promotes aqueous humor outflow and reduces aqueous humor production through vasoconstriction. It is primarily used in ophthalmic preparations to lower intraocular pressure. See also: Apraclodin (containing the active moiety). Apraclodin is an imidazoline compound with the chemical name 2-amino-4,5-dihydro-1H-imidazoline, in which one of the outer ring amino hydrogens is replaced by 4-amino-2,6-dichlorophenyl. It has multiple functions, including as an alpha-adrenergic agonist, antiglaucoma drug, ophthalmic drug, beta-adrenergic agonist, and diagnostic reagent. It belongs to the imidazoline, dichlorobenzene, and guanidine derivatives. It is the conjugate base of apraclon(1+). Apraclon, also known as iodopyridine, is a sympathomimetic drug used to treat glaucoma. It is an α2-adrenergic agonist. Apraclon is an α-adrenergic agonist. The mechanism of action of apraclon is as an α-adrenergic agonist. Apraclon is a clonidine derivative with selective α2-adrenergic agonist activity. After intraocular administration, apraclonidine reduces intraocular pressure (IOP) by increasing aqueous humor outflow through the uvea and sclera and reducing aqueous humor production through vasoconstriction. See also: apraclonidine hydrochloride (salt form). Indications: Used to prevent or reduce increases in intraocular pressure (IOP) before and after laser eye surgery, especially for prophylactic use. It can also be used as short-term adjuvant therapy for open-angle glaucoma patients who have received the maximum tolerated dose of medication but still require further reduction of intraocular pressure.
FDA Label

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Mechanism of Action
Apraclodin is a relatively selective α2-adrenergic receptor agonist with less stimulation of α1 receptors. Its intraocular pressure-lowering effect peaks two hours after administration. The exact mechanism of action of apraclodin is unclear, but animal and human fluorophotometric studies have shown that apraclodin has a dual mechanism of action: on the one hand, it reduces aqueous humor production by constricting the afferent vessels of the ciliary processes, and on the other hand, it increases uveal-scleral outflow.

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Transient ptosis is a known complication of botulinum toxin (BoNT) injections, caused by accidental migration of the toxin to the levator palpebrae superioris muscle. There is currently no treatment for ptosis caused by BoNT. Apraclodin hydrochloride is a topical eye drop with selective α2-receptor agonist activity and weak α1-receptor agonist activity, capable of lifting the eyelid. Apraclodin has been used as a diagnostic test for Horner's syndrome. We evaluated the efficacy of apraclodin in a group of patients with BoNT-induced ptosis and one patient with Horner's syndrome. Two drops of 0.5% apraclodin solution were instilled into the eye with ptosis in each patient, and the patient was re-examined after 20-30 minutes. Ptosis symptoms improved in all 6 patients. Ptosis symptoms also improved in one patient with Horner's syndrome. Apraclodin may be used not only for the diagnosis of Horner's syndrome, but also as an effective and safe treatment for BoNT-induced ptosis. [1]

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We investigated the acute effects of the intraocular pressure-lowering drug apraclodin (AP) on intraocular pressure (IOP) and aqueous humor dynamics in anesthetized rats during infusion-induced intraocular hypertension. The anterior chamber of the eye was infused twice: once at a constant rate of 0.05 μL/min and the other at a periodic rate of 0.25 μL/min, with the infusion pump turned on for 4 minutes and then off for 4 minutes. Data were processed using complex demodulation and second-order transfer function analysis. This allowed us to separately calculate the resistance components (Ao), namely trabecular meshwork and uveal-scleral outflow, and residual pressure (RP), the latter used to estimate the non-resistance components, namely aqueous humor synthesis and suprascleral venous pressure. We tested balanced salt solution (BSS) and artificial tears (AP, 0.0005%). AP significantly delayed the rise in intraocular pressure (IOP) within the groups: 20 minutes in the BSS group and 60 minutes in the AP group (p < 0.001). IOP in the AP group rats was lower than that in the control group within 100 minutes (p < 0.05). Ao increased in both groups after infusion (p < 0.05). AP initially had a transient inhibitory effect (p < 0.05). RP increased in both groups after infusion. AP had a strong inhibitory effect over the first 8 cycles (p < 0.05). These data suggest that the acute effect of AP in the rat model of ocular hypertension is to delay the rise in IOP, primarily by reducing the non-resistance components of aqueous humor dynamics. The resistance mechanism also showed transient inhibition. [2]

C9H11CL3N4

281.5694

280.005

C, 38.39; H, 3.94; Cl, 37.77; N, 19.90

73218-79-8

Apraclonidine;66711-21-5; 73218-79-8 (HCl); 73217-88-6

51763

Off-white to light yellow solid powder

1.63 g/cm3

395.5ºC at 760 mmHg

>230ºC

193ºC

3.167

4

2

2

16

247

0

OTQYGBJVDRBCHC-UHFFFAOYSA-N

InChI=1S/C9H10Cl2N4.ClH/c10-6-3-5(12)4-7(11)8(6)

2,6-dichloro-N1-(4,5-dihydro-1H-imidazol-2-yl)benzene-1,4-diamine hydrochloride

4-Aminoclonidine; Apraclonidina; APRACLONIDINE HYDROCHLORIDE; 73218-79-8; Apraclonidine HCl; p-Aminoclonidine hydrochloride; 2,6-dichloro-N1-(4,5-dihydro-1H-imidazol-2-yl)benzene-1,4-diamine hydrochloride; Iopidine; NC 14 hydrochloride; ALO-2145; Iopidine; P-aminoclonidine; Apraclonidinum

2934.99.9001

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.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~443.94 mM)
H2O : ≥ 12.5 mg/mL (~44.39 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (7.39 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.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (7.39 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.

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 (Please use freshly prepared in vivo formulations for optimal results.)