Naphazoline targets α₁- and α₂-adrenergic receptors. It provides balanced α₁/α₂ agonism. By binding to alpha-1 adrenoreceptors in blood vessels, it causes vasoconstriction. It also binds to I₁-imidazoline sites with a pKi of 6.61. Naphazoline reduces vascular hyperpermeability and promotes vasoconstriction. It reduces the levels of inflammatory factors (TNF-α, IL-1β and IL-6).

In vitro, Naphazoline functions as a direct-acting agonist at both α₁- and α₂-adrenergic receptors. It demonstrates binding to I₁-imidazoline sites with a pKi of 6.61. The compound reduces vascular hyperpermeability and promotes vasoconstriction. It reduces the levels of inflammatory factors (TNF-α, IL-1β and IL-6), cytokines (IFN-γ and IL-4). Detailed in vitro data are available in the primary literature.

Through effects on inflammation, NGF, and VEGF, napazoline (0.2 mg/kg, 10 µl per eye; IP, once) decreases conjunctivitis and conjunctival vascular hyperpermeability in mice produced by histamine or antigen [1].
In vivo, Naphazoline is used as a decongestant for the treatment of rhinitis and conjunctivitis. It is a vasoconstrictor with a rapid action in reducing swelling when applied to mucous membranes. It acts on alpha-receptors in the arterioles of the conjunctiva to produce constriction, resulting in decreased congestion. Naphazoline is a clinically used topical decongestant.

In vitro receptor binding assays for Naphazoline typically use membrane preparations from cells expressing α₁- or α₂-adrenergic receptors. Radioligand binding is performed using [³H]-prazosin (α₁) or [³H]-clonidine (α₂) as tracers. Membranes are incubated with radioligand and varying concentrations of Naphazoline in assay buffer at room temperature for 60-90 minutes. Nonspecific binding is determined using excess phentolamine. Bound radioactivity is measured by filtration and scintillation counting. Ki values are calculated from competition curves. Functional assays measure receptor-mediated calcium mobilization or cAMP inhibition.

For cell-based assays, cells expressing α₁- or α₂-adrenergic receptors are cultured in appropriate medium. Cells are seeded in 96-well plates and loaded with calcium-sensitive dye. Cells are treated with Naphazoline at various concentrations (0.001-100 μM) and calcium flux is measured. For α₂ receptors, cAMP inhibition is measured after forskolin stimulation. IC₅₀ and EC₅₀ values are calculated from dose-response curves. Cell viability is assessed by standard assays. All treatments include vehicle controls and are performed in triplicate.

Animal/Disease Models: Female wild-type balb/c (Bagg ALBino) mouse (4-5 weeks, 18±2g, n=8/group, using histamine or antigen (ovalbumin) to establish allergic conjunctivitis mouse model) [1]
Doses: 0.2mg/mL, 10 µl per eye
Route of Administration: intraperitoneal (ip) injection, once
Experimental Results: Dramatically inhibited conjunctival dye leakage in mice with histamine- or antigen-induced conjunctival vascular hyperpermeability. Reduces inflammatory responses and levels of IL-1β, IL-6, IFN-γ, and IL-4. Reduces the levels of IgE, GMCSF, NGF and VEGF in mice with antigen-induced conjunctival vascular hyperpermeability.
In vivo, Naphazoline is typically administered topically as eye drops or nasal spray. For animal studies, the compound is applied topically at various concentrations. Endpoints include vasoconstriction (reduced blood flow), reduced congestion, and reduced inflammation. Ocular or nasal tissue may be collected for histology. Blood samples may be collected for pharmacokinetic analysis. All procedures follow institutional guidelines.

Absorption, Distribution and Excretion
Absorption data for naphazoline are limited, but imidazoline compounds are generally weakly basic and lipophilic, exhibiting high bioavailability in the gastrointestinal tract. Imidazolinon compounds undergo partial hepatic metabolism, but most doses are likely excreted unchanged in the urine. Higher urine acidity leads to higher urinary excretion. Distribution data for naphazoline are limited, but imidazoline compounds are distributed throughout the body and can cross the blood-brain barrier. Clearance data for naphazoline are currently unavailable. Metabolism/Metabolites Metabolism data for naphazoline are limited. Imidazolinon compounds undergo partial hepatic metabolism, but most doses are likely excreted unchanged in the urine. Biological Half-Life The half-life is not yet determined, but the effect lasts 4 to 8 hours. The half-lives of other imidazoline compounds range from 2 to 12 hours.
Naphazoline (Naphthazoline, MW 210.27, C₁₄H₁₄N₂) is an α-adrenergic receptor agonist. The compound is a vasoconstrictor. It is used as a topical decongestant. Detailed pharmacokinetic parameters are available from pharmacological literature. The compound is typically applied topically with minimal systemic absorption. It is a clinically used pharmaceutical agent.

Protein Binding
Protein binding data for naphazoline is unavailable.
Naphazoline is a clinically used decongestant with an established safety profile. Common side effects include local irritation and rebound congestion with prolonged use. It is contraindicated in patients with narrow-angle glaucoma. It is available as an over-the-counter pharmaceutical product.

[1]. Treatment with olopatadine and naphazoline hydrochloride reduces allergic conjunctivitis in mice through alterations in inflammation, NGF and VEGF. Mol Med Rep. 2016 Apr;13(4):3319-25.

[2]. Central and peripheral adrenergic mechanisms regulating gastric secretion in the rat. J Pharmacol Exp Ther. 1977 Oct;203(1):125-31.

2-(1-Naphthylmethyl)-4,5-dihydro-1H-imidazol belongs to the naphthalene family of compounds. Naphazoline is a fast-acting imidazoline sympathomimetic vasoconstrictor that constricts small arteries in the eye or nasal cavity. It relieves congestion and is commonly found in many over-the-counter (OTC) eye drops and nasal preparations. Naphazoline was originally developed in 1942 as a nasal preparation for the treatment of nasal congestion. Naphazoline is an imidazoline derivative and a direct-acting sympathomimetic amine with vasoconstrictive activity. After being instilled into the eye, naphazoline exerts its effect by acting on α-adrenergic receptors in the conjunctival arterioles, causing vasoconstriction, thereby reducing conjunctival congestion and relieving itching, irritation, and redness. An adrenergic vasoconstrictor used as a decongestant. See also: Naphazoline hydrochloride (salt form). Drug Indications Naphazoline can be used as an over-the-counter eye drop for the treatment of ocular vasoconstriction, or as a nasal preparation for the treatment of nasal congestion. Mechanism of Action Naphazoline is a vasoconstrictor that works by stimulating alpha-adrenergic receptors in arterioles, thereby reducing congestion at the administration site. Naphazoline induces the release of norepinephrine from the sympathetic nervous system. Norepinephrine binds to alpha-adrenergic receptors, causing vasoconstriction. Naphazoline is also a weak beta-adrenergic receptor agonist, causing rebound vasodilation after alpha-adrenergic stimulation ends. The norepinephrine released by naphazoline can also trigger a negative feedback loop, thereby reducing norepinephrine production. Long-term use of naphazoline followed by discontinuation may lead to drug-induced rhinitis.

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Pharmacodynamics
Naphazoline is a sympathomimetic alpha-adrenergic agonist that constricts small arteries in the nasal cavity or eye, thereby reducing congestion at the administration site.
Naphazoline (Naphthazoline) is a clinically used topical decongestant for the treatment of rhinitis and conjunctivitis. It is a potent α-adrenergic receptor agonist. It reduces vascular hyperpermeability and promotes vasoconstriction. It is available as a pharmaceutical product and from chemical suppliers for research purposes. Its mechanism involves α-adrenergic receptor agonism and vasoconstriction.

C14H14N2

210.27436

210.115

835-31-4

Naphazoline nitrate;5144-52-5;Naphazoline hydrochloride;550-99-2;Naphazoline-d4 hydrochloride

4436

Typically exists as solid at room temperature

1.2±0.1 g/cm3

440.5±24.0 °C at 760 mmHg

254ºC

220.2±22.9 °C

0.0±1.0 mmHg at 25°C

1.640

3.88

1

1

2

16

272

0

N1CCNC=1CC1C2C(=CC=CC=2)C=CC=1

CNIIGCLFLJGOGP-UHFFFAOYSA-N

InChI=1S/C14H14N2/c1-2-7-13-11(4-1)5-3-6-12(13)10-14-15-8-9-16-14/h1-7H,8-10H2,(H,15,16)

2-(naphthalen-1-ylmethyl)-4,5-dihydro-1H-imidazole

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.

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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).

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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)

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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).

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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

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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.

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