IL-1β; IL-6; IL-4
α-adrenergic receptor [2]

Naphazoline hydrochloride (0.2 mg/kg, 10 µl per eye; IP, once) inhibits conjunctivitis in mice by reducing inflammation, NGF, and VEGF, as well as histamine- or antigen-induced conjunctival vascular hyperpermeability[1].

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In a mouse model of ovalbumin (OVA)-induced allergic conjunctivitis, topical ocular administration of Naphazoline HCl (alone or in combination with olopatadine) significantly alleviated allergic inflammatory responses. It reduced the number of conjunctival eosinophils by 42% compared to the untreated allergic control group [1]
- Naphazoline HCl treatment (topical) decreased the levels of pro-inflammatory cytokines in conjunctival tissues: TNF-α by 38%, IL-4 by 35%, and IL-13 by 32% compared to the control group. It also reduced the expression of nerve growth factor (NGF) by 40% and vascular endothelial growth factor (VEGF) by 36% [1]
- The combination of Naphazoline HCl and olopatadine exhibited a synergistic effect, with greater reduction in eosinophil infiltration (58%) and cytokine levels (TNF-α: 52%, IL-4: 48%, IL-13: 45%) compared to either drug alone [1]

Female wild-type BALB/c mice (4-5 weeks, 18 ± 2 g, n=8/group, allergic conjunctivitis mouse model established using histamine or an antigen (ovalbumin))
0.2 mg/mL, 10 µl per eye
Intraperitoneal injection (IP), once

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Allergic conjunctivitis model establishment: Female BALB/c mice were sensitized by intraperitoneal injection of OVA emulsified with adjuvant on days 0 and 7. On day 14, mice were challenged with OVA solution via topical ocular instillation to induce allergic conjunctivitis [1]
- Drug administration: Mice were randomly divided into four groups: normal control, allergic control, Naphazoline HCl alone (topical, 0.1% solution), and Naphazoline HCl + olopatadine (topical, 0.1% + 0.1% solution). Drugs were administered 30 minutes before OVA challenge and once daily for 7 consecutive days [1]
- Sample collection and detection: On day 21, mice were sacrificed, and conjunctival tissues were dissected. Eosinophil infiltration was observed by hematoxylin-eosin (HE) staining. Cytokine (TNF-α, IL-4, IL-13), NGF, and VEGF levels were quantified by ELISA [1]

Absorption, Distribution and Excretion
Following topical application of naphazoline hydrochloride solution to the conjunctiva, local vasoconstriction typically occurs within 10 minutes and can last for 2–6 hours. Occasionally, naphazoline may be absorbed sufficiently to produce systemic effects. Information regarding the distribution and elimination of this drug in the human body is currently unavailable.

Interactions
Patients receiving monoamine oxidase (MAO) inhibitors may experience severe hypertension if they take sympathomimetic drugs concurrently. Although there are no reports of naphazoline causing such reactions, the possibility of this interaction should be considered. Maprotiline or tricyclic antidepressants may enhance the pressor effect of naphazoline when used in combination with naphazoline hydrochloride. Pentobarbital appears to enhance the hypotensive effect of α-sympathomimetic drugs, including naphazoline hydrochloride. Non-human Toxicity Values Subcutaneous LD50 in rats: 385 mg/kg

[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.

Naphazoline is an organic molecular entity. Naphazoline hydrochloride is the hydrochloride salt form of naphazoline, an imidazole derivative and a direct sympathomimetic amine with vasoconstrictive effects. When used in the eye, naphazoline hydrochloride exerts its effects by acting on α-adrenergic receptors in the conjunctival arterioles, causing vasoconstriction, thereby reducing conjunctival congestion and relieving itching, irritation, and redness. It is an adrenergic vasoconstrictor used as a decongestant. See also: naphazoline (with active moiety); naphazoline hydrochloride; beniramine maleate (ingredient); antazoline phosphate; naphazoline hydrochloride (ingredient)...see more...

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Mechanism of Action
Naphazoline constricts the conjunctival vascular system. It is speculated that this effect is due to the drug directly stimulating α-adrenergic receptors in the conjunctival arterioles, thereby reducing conjunctival congestion. The mechanism of action of naphazoline is not fully understood. Most pharmacologists believe that this drug directly stimulates alpha-adrenergic receptors in the sympathetic nervous system, with little effect on beta-adrenergic receptors. Topical application of naphazoline to the conjunctiva causes arteriolar constriction, temporarily relieving conjunctival congestion, but reactive congestion may occur. This drug may also cause mydriasis when used on the conjunctiva, but this effect is usually minimal at concentrations used as an ocular decongestant.

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Therapeutic Uses
Adrenergic alpha receptor agonist; Nasal decongestant
Topical application of naphazoline to the conjunctiva provides temporary relief from congestion, itching, and mild irritation. Ocular decongestants are ineffective against delayed-type hypersensitivity reactions (e.g., contact dermatoconjunctivitis). The vasoconstrictive effect of naphazoline can be used in certain ophthalmic diagnostic procedures, but some clinicians prefer to use phenylephrine instead of naphazoline for such procedures. Commercially available ophthalmic solutions contain naphazoline and can be used in combination with antihistamines (such as antazoline phosphate or beniramine maleate) and/or astringents (such as zinc sulfate). At commonly used concentrations, zinc sulfate has relatively poor disinfection effects and may promote vasodilation. Adrenergic (vasoconstrictor); decongestant. Naphazoline hydrochloride (0.1%) is an imidazole derivative with preferential α2 receptor activity. In this study, naphazoline was instilled into 17 eyes of 12 patients with myopathy-related ptosis due to levator palpebrae superioris muscle involvement to selectively stimulate Müller's smooth muscle. Naphazoline significantly widened the palpebral fissure, with little change in pupil diameter, and no significant changes in intraocular pressure, visual acuity, or near point visual acuity. However, its efficacy diminished after several weeks of regular daily use, possibly due to rapid tolerance. In summary, naphazoline has significant cosmetic and functional efficacy for mild to moderate myogenic ptosis, especially in cases of occasional use. Drug Warnings Ophthalmic naphazoline may occasionally cause systemic sympathomimetic effects, such as headache, hypertension, arrhythmia, nervousness, nausea, dizziness, weakness, and sweating. Ophthalmic naphazoline may cause blurred vision, mild and transient stinging and/or irritation, mydriasis, and increased or decreased intraocular pressure. Conjunctival application of naphazoline, especially in elderly patients using high concentrations, may release pigment granules, presumably from the iris. Rebound congestion, characterized by reactive hyperemia, is common with prolonged use and may lead to drug overdose. For these reasons, prolonged use of this drug should be avoided. Patients receiving therapeutic doses of naphazoline hydrochloride ophthalmic solution have a lower probability of experiencing serious adverse reactions. When naphazoline hydrochloride is used in combination preparations, the precautions for each component in the preparation must be followed. Overuse and/or prolonged or excessive use may irritate the conjunctiva, especially in children, and may lead to adverse systemic reactions.
Patients with hypertension, cardiovascular disease, diabetes, hyperthyroidism, infection, or injury should use naphazoline hydrochloride eye drops with caution.
For more complete data on drug warnings for naphazoline hydrochloride (14 in total), please visit the HSDB record page.

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Naphazoline hydrochloride is a selective α-adrenergic receptor agonist with vasoconstrictive and anti-inflammatory properties[1].
- Its mechanism of action in allergic conjunctivitis includes reducing vascular permeability and inhibiting the release of pro-inflammatory cytokines NGF and VEGF, thereby reducing edema, redness, and inflammatory cell infiltration[1].
- It is often used for local relief of allergic conjunctivitis symptoms and can enhance the therapeutic effect when used in combination with antihistamines such as olopatadine[1].

C14H15CLN2

246.74

246.092

C, 68.15; H, 6.13; Cl, 14.37; N, 11.35

550-99-2

Naphazoline nitrate; 5144-52-5; Naphazoline; 835-31-4

11079

White to off-white solid powder

1.15 g/cm3

440.5ºC at 760 mmHg

254-260 °C

220.2ºC

2.95

2

1

2

17

272

0

C1(CC2=NCCN2)=CC=CC3=CC=CC=C13.Cl

DJDFFEBSKJCGHC-UHFFFAOYSA-N

InChI=1S/C14H14N2.ClH/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);1H

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

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.13 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 25.0 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: ≥ 2.5 mg/mL (10.13 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 25.0 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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Solubility in Formulation 3: ≥ 2.5 mg/mL (10.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 75 mg/mL (303.96 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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