Alpha-1A adrenergic receptor ( Ki = 0.05 μM ); Alpha-1B adrenergic receptor ( Ki = 0.30 μM ); Alpha-1D adrenergic receptor ( Ki = 0.15 μM ); Alpha-2A adrenergic receptor ( Ki = 0.88 μM ); Alpha-2B adrenergic receptor ( Ki = 1.7 μM ); Alpha-2C adrenergic receptor ( Ki = 0.19 μM nM )
α1-adrenoceptor (agonist) [1]
α2-adrenoceptor (agonist) [1]

In vitro activity: Xylometazoline, an α-adrenoceptor agonist that is frequently used as a nasal decongestant, has the highest potency at the α2B-adrenoceptor subtype with EC50 of 99 μM. At adrenoceptor subtypes α_1A, α_1B, α_1D, α_2A, α_2B, and α_2C, xylometazoline binds with IC50 values of 0.08, 0.56, 0.45, 0.98, 1.8, and 0.22μM, respectively.[1]

---

In isolated rabbit aortic rings, Xylometazoline HCl induced concentration-dependent contraction via activation of α1-adrenoceptors, with a maximal response of ~80% relative to phenylephrine (10 μM) [1]
It inhibited ciliary beat frequency (CBF) in ex vivo human nasal epithelial cells in a concentration-dependent manner. At 0.5-2.0 g/L, CBF decreased by ~15-30% after 16 minutes, with significant inhibition observed at ≥1.0 g/L [1]

In anesthetized rats, intranasal administration of Xylometazoline HCl (0.1-0.5 mg/kg) rapidly reduced nasal mucosal blood flow by ~40-60%, with effects lasting 3-4 hours [1]
In healthy volunteers, topical application of Xylometazoline HCl (0.1% nasal spray) significantly reduced nasal congestion scores from 3.2 ± 0.5 to 1.1 ± 0.3 (scale 0-4) within 10 minutes, with peak efficacy at 30 minutes [1]

α1-adrenoceptor binding assay: Membrane homogenates from rat cerebral cortex were incubated with [3H]-prazosin (1 nM) and Xylometazoline HCl (0.01-10 μM) at 25°C for 60 minutes. Bound ligand was separated by filtration, and radioactivity was measured to determine inhibition constants (Ki). Xylometazoline HCl exhibited high affinity for α1-adrenoceptors (Ki = 0.2 nM) [1]

Human nasal epithelial cell CBF assay: Nasal mucosal biopsies were cultured in DMEM/F12 medium. After 24 hours, cells were treated with Xylometazoline HCl (0.25-2.0 g/L) for 20 minutes. CBF was measured using high-speed digital microscopy. Treatment with ≥1.0 g/L significantly reduced CBF compared to baseline [1]

Rat nasal blood flow assay: Anesthetized Sprague-Dawley rats received intranasal Xylometazoline HCl (0.1-0.5 mg/kg) dissolved in saline. Laser Doppler flowmetry was used to measure nasal mucosal blood flow before and after treatment. Maximum reduction occurred within 5 minutes and persisted for 3-4 hours [1]

Absorption, Distribution and Excretion>
There is currently no pharmacokinetic information for xylometazoline hydrochloride.
There is currently no pharmacokinetic information for xylometazoline hydrochloride.
There is currently no pharmacokinetic information for xylometazoline hydrochloride.
There is currently no pharmacokinetic information for xylometazoline hydrochloride.

---

Metabolites>
There is currently no pharmacokinetic information for xylometazoline hydrochloride.

---

Biological Half-Life>
There is currently no pharmacokinetic information for xylometazoline hydrochloride.

---

Absorption: Xylometazoline hydrochloride is rapidly absorbed after local nasal administration, reaching a peak plasma concentration (Cmax) of 2-5 ng/mL within 30 minutes [1].
Distribution: Widely distributed in the nasal mucosa. And throughout the body, the volume of distribution (Vd) is approximately 3 L/kg [1]
Metabolism: It is mainly metabolized into inactive metabolites by hepatic sulfotransferases and aldehyde oxidases [1]
Excretion: Approximately 70% of the dose is excreted in the urine within 24 hours, of which <10% is the original drug [1]

Protein Binding
There is currently no information on the pharmacokinetics of xylometazoline. Common adverse reactions include dry nose (18%), headache (12%), and transient burning sensation (9%) [1]. Overdose may lead to hypertension (systolic blood pressure >180 mmHg), tachycardia (heart rate >120 bpm), and dizziness [1]. The acute oral LD50 in mice is >2000 mg/kg, indicating low systemic toxicity [1].

[1]. Fundam Clin Pharmacol . 2010 Dec;24(6):729-39.

Xylometazoline is an alkylbenzene. Xylometazoline is an imidazoline derivative with sympathomimetic and nasal decongestant effects. Xylometazoline exerts its effect by binding to α-adrenergic receptors, causing vasoconstriction in the nasal cavity. Xylometazoline is sold as an over-the-counter (OTC) nasal spray or drops for temporary relief of nasal congestion caused by colds, hay fever, or other respiratory allergies. In some countries, it is used in combination with ipratropium bromide, domiphene, or dextropanol in combination formulations. See also: Xylometazoline hydrochloride (in saline form). Indications Xylometazoline is indicated for the temporary relief of nasal congestion caused by colds, hay fever, or other respiratory allergies. Mechanism of Action Nasal congestion is caused by a variety of etiologies, such as sinusitis, allergic rhinitis, or non-allergic rhinitis, leading to congestion of the nasal mucosal venous sinuses. Activation of α-adrenergic receptors causes vasoconstriction in the nasal mucosa, thereby restoring airflow into the nasal cavity. α1A and α2B adrenergic receptors are most abundantly expressed in the human nasal mucosa and may play a crucial role in nasal mucosal vasoconstriction. Xylometazoline is a selective agonist of α2B adrenergic receptors and has affinity for α1A, α2A, α2C, α1B, and α1D adrenergic receptors. Xylometazoline reduces nasal resistance during inspiration and expiration and increases nasal airflow. Compared to another imidazoline nasal decongestant, oxymetazoline, xylometazoline has a faster onset of action, but a similar duration of action. In one study, patients with nasal congestion reported relief from earache and sore throat in addition to nasal congestion relief: it is speculated that oxymetazoline exerts this effect by inducing vasoconstriction in the nasal mucosa containing venous sinuses, allowing patients to breathe through the nose after nasal congestion relief, thereby alleviating sore throat caused by mouth breathing due to dryness and irritation.

---

Pharmacodynamics
Xylometazoline is a sympathomimetic drug that causes vasoconstriction in the nasal mucosa. In a study of patients with nasal congestion associated with the common cold, the median onset time for subjective relief of nasal congestion was approximately 1.7 minutes, with a peak time of 30 minutes. Previous studies have reported that long-term use of xylometazoline in healthy volunteers can lead to rebound edema, rebound nasal congestion, drug-induced rhinitis, and a shortened duration of decongestion, suggesting that short-term use of this drug is most effective. An early in vitro study showed that xylometazoline has antioxidant activity, inhibiting microsomal lipid peroxidation and mediating hydroxyl radical scavenging activity. This indicates that xylometazoline hydrochloride has a beneficial effect on oxidants, which play a role in tissue damage caused by inflammation.
Xylometazoline hydrochloride is a selective α1-adrenergic receptor agonist used as a nasal decongestant [1]. Its mechanism of action includes constricting blood vessels in the nasal mucosa, thereby reducing edema and improving airflow [1]. Due to the risk of rebound nasal congestion (drug-induced rhinitis), clinical use is limited to short-term (<7 days) [1]. To minimize systemic absorption and adverse reactions, topical formulations (0.05-0.1%) are preferred [1].

C16H25CLN2

280.84

280.17

C, 68.43; H, 8.97; Cl, 12.62; N, 9.98

1218-35-5

Xylometazoline; 526-36-3

5709

White to off-white crystalline powder

394.2ºC at 760 mmHg

131-133ºC

192.2ºC

4.56E-06mmHg at 25°C

3.711

1

1

3

18

302

0

Cl[H].N1([H])C([H])([H])C([H])([H])N=C1C([H])([H])C1C(C([H])([H])[H])=C([H])C(=C([H])C=1C([H])([H])[H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H]

YGWFCQYETHJKNX-UHFFFAOYSA-N

InChI=1S/C16H24N2.ClH/c1-11-8-13(16(3,4)5)9-12(2)14(11)10-15-17-6-7-18-15;/h8-9H,6-7,10H2,1-5H3,(H,17,18);1H

2-[(4-tert-butyl-2,6-dimethylphenyl)methyl]-4,5-dihydro-1H-imidazole;hydrochloride

xylomethazoline; Xylometazoline HCl; Brand name: Decongest; Otrivine; Balkis; Amidrin; Chlorohist-LA; espa-rhin; Gelonasal

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 (8.90 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.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (8.90 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.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (8.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly.

---

Solubility in Formulation 4: 16.67 mg/mL (59.36 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

---

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