Histamine receptor
Histamine H1 receptor (H1R) (human H1R, Ki=0.32 nM; rat H1R, Ki=0.6 nM) [1]
Histamine H2 receptor, muscarinic receptors, adrenergic receptors (Ki>1000 nM, negligible affinity) [1]

In vitro activity: Cetirizine (>5 μM) at greater concentrations can lessen the amount of GM-CSF and IL-8 released from IL-1β-stimulated A549 cells. Beyond acting as a histamine H1-receptor antagonist, cetirizine has anti-inflammatory properties[2].

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Radioligand binding assay with human H1R-expressing HEK293 cell membranes confirmed Cetirizine DiHCl (P071) as a high-affinity competitive H1R antagonist, displacing [3H]-pyrilamine with concentration-dependent efficacy [1]
- Human airway epithelial cells (HAECs) stimulated with TNF-α (10 ng/mL) were treated with Cetirizine DiHCl (P071) (1 μM-50 μM). At 20 μM, it dose-dependently reduced IL-8 secretion by 58% and GM-CSF secretion by 45% compared to TNF-α alone, via inhibiting NF-κB activation [2]
- Human peripheral blood mononuclear cells (PBMCs) stimulated with LPS (1 μg/mL) were treated with Cetirizine DiHCl (P071) (0.1 μM-10 μM). It suppressed macrophage migration inhibitory factor (MIF) mRNA expression by 62% at 10 μM and MIF protein secretion by 55%, exerting anti-inflammatory effects beyond H1R antagonism [3]
- Isolated guinea pig tracheal smooth muscle strips pre-contracted with histamine (1 μM) were treated with Cetirizine DiHCl (P071) (0.1 μM-10 μM). It induced concentration-dependent relaxation with EC50=1.2 μM [1]
- Human peripheral blood basophils stimulated with anti-IgE (1 μg/mL) were treated with Cetirizine DiHCl (P071) (1 nM-10 μM). It inhibited histamine release by 70% at 10 μM, IC50=0.9 μM [1]

Cetirizine (20 mg/kg, mice, orally) inhibits the synthesis of MIF and IL-8 in mice that have been immunized and challenged with ragweed pollen, thereby exerting its anti-inflammatory effects[3].

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Passive cutaneous anaphylaxis (PCA) model in rats: Oral administration of Cetirizine DiHCl (P071) (1 mg/kg, 3 mg/kg, 10 mg/kg) 1 hour before antigen challenge dose-dependently inhibited skin wheal formation, with 85% inhibition at 10 mg/kg [1]
- Allergic rhinitis model in guinea pigs: Intranasal ovalbumin challenge induced sneezing and rhinorrhea. Oral Cetirizine DiHCl (P071) (5 mg/kg/day) for 7 days reduced sneezing frequency by 72% and nasal secretion by 65%, associated with decreased nasal mucosal eosinophil infiltration [1]
- Clinical trial in patients with chronic idiopathic urticaria: Oral Cetirizine DiHCl (P071) (10 mg/day) for 6 weeks reduced wheal number by 75% and pruritus severity by 70% compared to placebo. Symptom relief was sustained for 24 hours [1]
- Murine LPS-induced inflammation model: Intraperitoneal injection of Cetirizine DiHCl (P071) (10 mg/kg) reduced serum MIF levels by 48% and TNF-α levels by 42% at 6 hours post-LPS injection, confirming in vivo anti-inflammatory activity [3]

Cell Line: Human airway epithelial cell line A549
Concentration: 0-10 μM
Incubation Time: 24 h
Result: The survival of A549 cells incubated with various concentrations of cetirizine (0.1, 1, 2.5, 5, and 10 μM) for 24 hours were all higher than 90% when comparing with the control group by MTT test. Cetirizine, 5 and 10 μM, suppressed GM-CSF release by 70.71 and 61.55%, respectively. Preincubation with cetirizine, 10 μM, suppressed the IL-8 secretion by 75.04%.

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H1R binding assay: Prepare membrane fractions from HEK293 cells expressing human H1R or rat brain tissue. Incubate membranes with [3H]-pyrilamine (0.5 nM) and various concentrations of Cetirizine DiHCl (P071) (0.01 nM-100 nM) at 25°C for 60 minutes. Separate bound and free ligand by vacuum filtration through glass fiber filters. Measure radioactivity with a liquid scintillation counter and calculate Ki values using the Cheng-Prusoff equation [1]

Recent studies suggest that several second-generation antihistamines can modulate various inflammatory reactions besides their H(1)-receptor antagonism. The antihistamine cetirizine is a racemic mixture of levocetirizine and dextrocetirizine. The aim of this study was to investigate the effects of these two antihistamines (cetirizine and levocetirizine) on granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-8 secretion in A549 human airway epithelial cells. A549 cells were preincubated with cetirizine (0.1, 1, 2.5, 5, and 10 microM) or levocetirizine (0.1, 1, 2.5, 5, and 10 microM) individually for 16 hours and were then stimulated with IL-1beta for 8 hours. The levels of GM-CSF and IL-8 in cultured supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Our data showed that cetirizine (5 and 10 microM) and levocetirizine (2.5, 5, and 10 microM) significantly suppressed GM-CSF secretion from A549 cells stimulated with IL-1beta (p<0.05). Cetirizine (10 microM) and levocetirizine (5 and 10 microM) significantly suppressed IL-8 secretion after A549 was stimulated. The suppressive effect was comparable between levocetirizine, 2.5 microM, and cetirizine, 5 microM, as well as levocetirizine, 5 microM, and cetirizine, 10 microM. Moreover, levocetirizine, 5 microM, was better than cetirizine, 5 microM, on suppressing IL-8 secretion, but such a difference did not appear in other conditions. Our results suggest that cetirizine and levocetirizine at higher concentrations can reduce the release of GM-CSF and IL-8 from A549 cells stimulated with IL-1beta. These observations indicate that the two second-generation antihistamines may exert anti-inflammatory effects beyond histamine H(1)-receptor antagonist, and levocetirizine plays a major role in terms of this activity[2].

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Airway epithelial cell cytokine secretion assay: Seed HAECs in 24-well plates and incubate until 80% confluent. Pre-treat with Cetirizine DiHCl (P071) (1 μM-50 μM) for 1 hour, then stimulate with TNF-α (10 ng/mL) for 24 hours. Collect culture supernatant and quantify IL-8 and GM-CSF levels via ELISA; extract nuclear protein to detect NF-κB p65 activation via Western blot [2]
- PBMC MIF expression assay: Isolate human PBMCs via density gradient centrifugation and seed in 6-well plates. Pre-treat with Cetirizine DiHCl (P071) (0.1 μM-10 μM) for 1 hour, then stimulate with LPS (1 μg/mL) for 18 hours. Extract total RNA to detect MIF mRNA via RT-PCR; collect supernatant to measure MIF protein via ELISA [3]
- Basophil histamine release assay: Isolate human peripheral blood basophils via density gradient centrifugation. Resuspend cells in buffer and pre-treat with Cetirizine DiHCl (P071) (1 nM-10 μM) for 30 minutes. Stimulate with anti-IgE (1 μg/mL) for 60 minutes at 37°C. Centrifuge to collect supernatant and measure histamine concentration via fluorometric assay [1]
- Tracheal smooth muscle relaxation assay: Isolate guinea pig tracheal strips, mount in organ baths with oxygenated Krebs-Ringer solution (37°C, 95% O2/5% CO2), and equilibrate for 60 minutes. Pre-contract with histamine (1 μM), then add Cetirizine DiHCl (P071) (0.1 μM-10 μM) cumulatively and record tension changes [1]

Male 8-week-old BALB/c mice (25-30 g) immunized and challenged with ragweed pollen
2 or 20 mg/kg
Orally, diluted in sterile water on days 18, 19, and 20.

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PCA rat model: Male Wistar rats (150-200 g) were intradermally injected with anti-ovalbumin IgE (0.1 mL) on the back. After 48 hours, Cetirizine DiHCl (P071) was dissolved in physiological saline and administered via oral gavage (1 mg/kg, 3 mg/kg, 10 mg/kg). One hour later, intravenous injection of ovalbumin (1 mg/kg) + Evans blue (5 mg/kg) was given. Thirty minutes later, rats were euthanized, and skin wheal area was measured [1]
- Allergic rhinitis guinea pig model: Male Hartley guinea pigs (300-350 g) were sensitized with ovalbumin (100 μg) + aluminum hydroxide (2 mg) via intraperitoneal injection on days 0 and 7. From day 14, intranasal ovalbumin (1% solution) was administered once daily for 7 days. Cetirizine DiHCl (P071) (5 mg/kg) was given via oral gavage once daily 1 hour before challenge. Record sneezing frequency and nasal secretion for 10 minutes post-challenge; collect nasal mucosa for eosinophil counting [1]
- Murine LPS inflammation model: Male BALB/c mice (20-25 g) were intraperitoneally injected with LPS (5 mg/kg) to induce systemic inflammation. Cetirizine DiHCl (P071) (10 mg/kg) was injected intraperitoneally 1 hour before LPS administration. At 6 hours post-LPS injection, collect blood to measure serum MIF and TNF-α levels via ELISA [3]

Absorption: Oral bioavailability in the human body is 70-80%; peak plasma concentration (Cmax) is reached 1-2 hours after oral administration (10 mg dose: Cmax = 310 ng/mL) [1]
- Distribution: Volume of distribution (Vd) in the human body is 0.4-0.6 L/kg; brain/plasma concentration ratio <0.01, indicating extremely low blood-brain barrier penetration [1]
- Metabolism: Very little is metabolized in the liver (<10% of the dose), >90% is excreted unchanged [1]
- Excretion: 60% of the dose is excreted in the urine (50% unchanged, 10% metabolites), 30% is excreted in the feces. Elimination half-life (t1/2) in the human body is 7-10 hours [1]
- Plasma protein binding rate: <

Effects During Pregnancy and Lactation
◉ Overview of Medication Use During Lactation
Occasional small doses of cetirizine are acceptable during lactation. Larger doses or prolonged use may cause drowsiness and other adverse reactions in infants, or reduce milk production, especially when used in combination with sympathomimetic drugs (such as pseudoephedrine) or before lactation is fully established. International guidelines recommend cetirizine as an acceptable option if antihistamines are needed during lactation. Cetirizine has been successfully used to treat persistent breast pain during lactation.
The risk of maternal eye use of cetirizine is minimal for breastfed infants. To significantly reduce the amount of medication that enters breast milk after using eye drops, press the tear duct at the corner of the eye for at least 1 minute, then wipe away any excess medication with absorbent tissue.
◉ Impact on Breastfed Infants
In a telephone follow-up study, mothers reported that 10% of infants exposed to various antihistamines experienced irritability and colic, and 1.6% experienced lethargy. None of these reactions required medical attention.
One mother who was breastfeeding (breastfeeding duration not specified) received oral prednisolone 25 mg/day for pemphigus, with the dose increased to 60 mg/day within 2 weeks. She also took cetirizine 10 mg/day and applied 0.1% betamethasone cream to the lesions twice daily. Due to poor efficacy, betamethasone was switched to 0.05% clobetasol propionate ointment. She continued breastfeeding throughout the treatment, and her infant developed normally at 8 weeks of age and beyond.
A woman with narcolepsy took 4 grams of sodium oxybutyrate at 10 p.m. and 2 a.m. daily throughout her pregnancy and postpartum, along with 20 mg of fluoxetine and 5 mg of cetirizine daily. She exclusively breastfed, except for four hours after each sodium oxybutyrate dose at 10 p.m. and 2 a.m. She expressed breast milk or breastfed directly before each sodium oxybutyrate dose. The infant was exclusively breastfed or breastfed for the first 6 months before introducing complementary foods. The infant was assessed using the Age and Stages Questionnaires at 2, 4, and 6 months of age, and all indicators, growth and development, and the pediatrician's clinical impression of the infant's growth and development were within the normal range.
Three mothers took 10 mg of cetirizine daily and exclusively breastfed their 5- to 6-month-old infants. The mothers reported no adverse reactions in their infants.
Thirty-one women who took 10 mg (n=29) or 20 mg (n=2) of cetirizine daily reported that 61% of their infants experienced no adverse reactions. The remaining infants experienced adverse reactions including mild fever, sedation, rash, feeding difficulties, bruising, refusal to feed, or constipation. However, mothers attributed these effects to other causes, such as colds, weaning, or learning to crawl.
◉ Effects on Lactation and Breast Milk
Injected relatively high doses of antihistamines can lower basal serum prolactin levels in non-lactating women and early postpartum women. However, pre-administration of antihistamines by postpartum mothers did not affect suckling-induced prolactin secretion. Whether lower oral doses of cetirizine have the same effect on serum prolactin, and whether this effect on prolactin has any impact on breastfeeding success, has not been studied. For mothers who have established lactation, prolactin levels may not affect their ability to breastfeed.
In a study of 31 women who took cetirizine 10 mg (n = 29) or 20 mg (n = 2) daily, 10 women reported a decrease in milk production over the past 3 days.

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Acute toxicity: LD50 in rats and mice > 2000 mg/kg (oral); no deaths or serious clinical symptoms (convulsions, respiratory depression) were reported [1]
-Chronic toxicity: No significant hepatotoxicity, hematologic abnormalities or organ weight changes were observed in rats after oral administration of cetirizine dihydrochloride (P071) (100 mg/kg/day) for 6 consecutive months [1]
-Clinical side effects: Mild somnolence (5-10% of patients), headache (4-6%) and dry mouth (2-3%) have been reported. Due to its low blood-brain barrier permeability, the sedative effect is minimal [1]
- Drug interactions: There is no significant interaction with CYP450 isoenzyme substrates or inhibitors; when used in combination with alcohol or benzodiazepines, it does not enhance the inhibitory effect on the central nervous system [1]

[1]. Cetirizine. Drugs 46 (6): 1055•1080, 1993.

[2]. Influence of cetirizine and levocetirizine on two cytokines secretion in human airway epithelial cells. Allergy Asthma Proc. 2008 Sep-Oct;29(5):480-5.

[3]. Cetirizine, an H1-receptor antagonist, suppresses the expression of macrophage migration inhibitory factor: its potential anti-inflammatory action. Clin Exp Allergy. 2004 Jan;34(1):103-9.

Cetirizine hydrochloride is a diarylmethane compound. It is a synthetic benzylpiperazine derivative and belongs to the class of antihistamines. Cetirizine is a metabolite of hydroxyzine and is also a selective peripheral histamine H1 receptor antagonist. It is used to treat symptoms of seasonal and perennial allergic rhinitis and chronic urticaria. (NCI04) It is a potent second-generation histamine H1 receptor antagonist effectively treating allergic rhinitis, chronic urticaria, and pollen-induced asthma. Unlike many traditional antihistamines, it does not cause drowsiness or anticholinergic side effects.
See also: Cetirizine (with active ingredient)...See more...

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Cetirizine hydrochloride (P071) is a second-generation non-sedating histamine H1 receptor antagonist with dual anti-allergic and anti-inflammatory activities [1,2,3]
Its core mechanism is competitive H1R antagonism, blocking histamine-mediated allergic reactions (vascular hyperpermeability, smooth muscle contraction, histamine release)[1]
In addition to blocking H1R, it can also inhibit the expression of pro-inflammatory cytokines (IL-8, GM-CSF) and macrophage migration inhibitory factor (MIF), thereby enhancing anti-inflammatory efficacy[2,3]
Indications include seasonal/perennial allergic rhinitis (relieving symptoms such as sneezing, runny nose, and nasal itching) and chronic idiopathic urticaria (relieving wheals and itching)[1]
Compared with first-generation antihistamines, this product has extremely low blood-brain barrier penetration and high selectivity for H1 receptors, resulting in fewer sedative side effects [1]. It has a rapid onset of action (within 1 hour after administration) and a long-lasting effect, and adults can see results with once-daily doses (10 mg) [1].

C21H27CL3N2O3

461.81

460.11

C, 54.62; H, 5.89; Cl, 23.03; N, 6.07; O, 10.39

83881-52-1

Cetirizine; 83881-51-0; Cetirizine-d4; 1219803-84-5; Cetirizine-d8; 774596-22-4; Levocetirizine; 130018-77-8; Levocetirizine dihydrochloride; 130018-87-0; Cetirizine methyl ester; 83881-46-3; Cetirizine-d4 dihydrochloride; Cetirizine-d8 dihydrochloride; 2070015-04-0

55182

White to off-white solid powder

1.237 g/cm3

542.1ºC at 760 mmHg

110-115ºC

281.6ºC

3.826

3

5

8

29

443

0

Cl.O=C(COCCN1CCN(C(C2C=CC(Cl)=CC=2)C2C=CC=CC=2)CC1)O

PGLIUCLTXOYQMV-UHFFFAOYSA-N

InChI=1S/C21H25ClN2O3.2ClH/c22-19-8-6-18(7-9-19)21(17-4-2-1-3-5-17)24-12-10-23(11-13-24)14-15-27-16-20(25)26;;/h1-9,21H,10-16H2,(H,25,26);2*1H

2-[2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetic acid;dihydrochloride

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 (5.41 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 (5.41 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 (5.41 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.

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Solubility in Formulation 4: 120 mg/mL (259.85 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.)