 Chemical Structure.png)
Apraclonidine (iopidine) HCl, the hydrochloride salt of Apraclonidine, is a potent sympathomimetic acting as an alpha2-adrenergic agonist and is used in glaucoma therapy. It is also a weak alpha-1 adrenergic receptor agonist. Apraclonidine enhances aqueous humor uveoscleral outflow and decreases aqueous production by vasoconstriction.
Physicochemical Properties
| Molecular Formula | C9H11CL3N4 |
| Molecular Weight | 281.5694 |
| Exact Mass | 280.005 |
| Elemental Analysis | C, 38.39; H, 3.94; Cl, 37.77; N, 19.90 |
| CAS # | 73218-79-8 |
| Related CAS # | Apraclonidine;66711-21-5; 73218-79-8 (HCl); 73217-88-6 |
| PubChem CID | 51763 |
| Appearance | Off-white to light yellow solid powder |
| Density | 1.63 g/cm3 |
| Boiling Point | 395.5ºC at 760 mmHg |
| Melting Point | >230ºC |
| Flash Point | 193ºC |
| LogP | 3.167 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 16 |
| Complexity | 247 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | OTQYGBJVDRBCHC-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C9H10Cl2N4.ClH/c10-6-3-5(12)4-7(11)8(6) |
| Chemical Name | 2,6-dichloro-N1-(4,5-dihydro-1H-imidazol-2-yl)benzene-1,4-diamine hydrochloride |
| Synonyms | 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 |
| 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
| 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 hydrochloride is the hydrochloride salt of apraclonidine. It has a role as an alpha-adrenergic agonist and an antiglaucoma drug. It contains an apraclonidine. Apraclonidine Hydrochloride is the hydrochloride salt form of apraclonidine, a clonidine derivative with selective alpha-2-adrenergic agonistic property. When administered directly to eyes, apraclonidine hydrochloride enhances aqueous humor outflow and decreases aqueous production by vasoconstriction. It is used mostly in ophthalmic preparations for decreasing intraocular pressure. See also: Apraclonidine (has active moiety). 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. Transient ptosis is a known complication of botulinum toxin (BoNT) injection due to inadvertent migration of toxin into the levator palpebrae superioris muscle. Currently there is no treatment available for BoNT induced ptosis. Apraclonidine hydrochloride is a topical ophthalmic solution with selective alpha-2 and weak alpha-1 receptor agonist activity that has the ability to elevate the eye lid. Apraclonidine has been used as a diagnostic test in Horner's syndrome. We evaluated the effects apraclonidine in a cohort of BoNT induced ptosis and a patient with Horner syndrome. Each patient was administered 2 drops of apraclonidine 0.5% solution to the eye with the ptosis and was re-examined 20-30min later. All 6 patients showed improvement in ptosis. There was also improvement in ptosis in a patient with Horner's syndrome. Apraclonidine is not only useful as a diagnostic test in Horner's syndrome, but may be an effective and safe treatment for BoNT-induced ptosis.[1] We studied the acute effects of the ocular hypotensive drug, apraclonidine (AP), on intraocular pressure (IOP) and aqueous humor dynamics of anesthetized rats during infusion-induced ocular hypertension. Two infusions were made into the anterior chamber of the eye: one was constant at a rate of 0.05 microl/min, the other was cyclic, at a rate of 0.25 microl/min, with the pump on for 4 min, then off for 4 min. Data were processed by complex demodulation and analysis of a second-order transfer function. This permitted separate calculations of resistive components (Ao), i.e., trabecular meshwork and uveoscleral outflows, and residual pressure (RP) estimating nonresistive components, i.e., aqueous synthesis and episcleral venous pressure. A balanced salt solution (BSS) and AP (0. 0005%) were tested. AP markedly delayed the within-group rise in IOP: 20 min for BSS vs. 60 min for AP (p < 0.001). IOP of AP rats was less than control for 100 min (p < 0.05). The infusions raised Ao in both groups (p < 0.05). AP initially had a transient inhibitory effect (p < 0.05). Infusions raised RP in both groups. AP had a strong inhibitory effect for the first 8 cycles (p < 0.05). These data document that the acute effects of AP in this in vivo rat model of ocular hypertension were to delay increases in IOP, mainly by reducing nonresistive components of aqueous humor dynamics. Transient inhibition of resistive mechanisms also occurred. [2] |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~443.94 mM) H2O : ≥ 12.5 mg/mL (~44.39 mM) |
| Solubility (In Vivo) |
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. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5515 mL | 17.7576 mL | 35.5151 mL | |
| 5 mM | 0.7103 mL | 3.5515 mL | 7.1030 mL | |
| 10 mM | 0.3552 mL | 1.7758 mL | 3.5515 mL |