Levocetirizine Dihydrochloride

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Cat Number

API130018870

CAS Number

130018-87-0

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CAS Number

130018-87-0

EINECS

641-093-3

Storage

Store at room temperature

Synonyms

cetirizine (R)-form dihydrochloride; UCB-28556; NSC-758898; DTXSID30926567; CETIRIZINE HYDROCHLORIDE (R)-; (2-{4-[(R)-(4-Chlorophenyl)phenylmethyl]piperazin-1-yl}ethoxy)acetic acid dihydrochloride

Molecular Formula

C21H27Cl3N2O3

Molecular Weight

461.81

Smiles

C1CN(CCN1CCOCC(=O)O)[C@H](C2=CC=CC=C2)C3=CC=C(C=C3)Cl.Cl.Cl

Appearance

White to off-white solid

Melting Point

205-208°C (dec.)

Boiling Point

542.1±45.0°C at 760 mmHg (Predicted)

Relative Density

1.237±0.06 (Predicted)

General Description

Levocetirizine dihydrochloride is the (R)-enantiomer of cetirizine and the active optical isomer of the racemic mixture. It is a second-generation piperazine derivative antihistamine that carries a carboxylic acid group, making it zwitterionic at physiological pH. The dihydrochloride salt provides water solubility and stability. Levocetirizine has higher affinity for the histamine H1 receptor than the (S)-enantiomer.

Mechanism of Action

Levocetirizine acts as a highly selective, competitive antagonist at peripheral H1 histamine receptors. By blocking histamine binding, it prevents histamine-induced vasodilation, increased vascular permeability, and sensory nerve stimulation. Unlike first-generation antihistamines, it does not appreciably cross the blood-brain barrier due to the carboxylate group, resulting in minimal sedative effects. Its affinity for H1 receptors is approximately twice that of cetirizine.

Application

Levocetirizine is indicated for the relief of symptoms of seasonal and perennial allergic rhinitis (including nasal congestion, sneezing, rhinorrhea, and ocular itching) and chronic idiopathic urticaria. It has a rapid onset of action (within one hour) and sustained duration of 24 hours. The enantiomeric purity eliminates the inactive (S)-isomer, potentially reducing side effect burden and allowing lower dosing.

In a rat model of lipopolysaccharide (LPS)‑induced acute lung injury, oral levocetirizine (1 mg/kg/day for 7 days) significantly attenuated pulmonary edema, bronchoalveolar lavage fluid protein and lactate dehydrogenase levels, and leukocyte recruitment. It also reduced lung tissue and BALF TNF‑α, decreased malondialdehyde, and restored superoxide dismutase activity. Histological examination confirmed less tissue damage. Levocetirizine, a nonsedating H₁ antihistamine, exhibits anti‑inflammatory and antioxidant effects that protect against LPS‑induced lung injury, suggesting potential repurposing for acute respiratory distress syndrome.

Fig. 1 Effects of levocetirizine on serum C-reactive protein (CRP) levels in LPS-challenged rats. (Fahmi ANA, et al., 2018)

References

Fahmi ANA, et al. Levocetirizine Pretreatment Mitigates Lipopolysaccharide-Induced Lung Inflammation in Rats. Biomed Res Int. 2018;2018:7019759.

In a double‑blind, three‑way crossover study (18 healthy young men), levocetirizine 5 mg and diphenhydramine 50 mg were compared with placebo. Diphenhydramine significantly impaired Stroop test accuracy and reduced prefrontal hemodynamic responses (oxygenated hemoglobin) while increasing prefrontal glucose consumption (PET), indicating uncoupling of metabolism and perfusion. Levocetirizine did not impair cognitive performance. Subjective sleepiness did not differ between groups. Antihistamines may disrupt normal neurovascular coupling, potentially via increased energy demand and suppressed capillary permeability.

Fig. 2 Results of voxel‐by‐voxel statistical parametric analysis of positron emission tomography images with [18F]fluorodeoxyglucose. (Kikuchi A, et al., 2018)

References

Kikuchi A, et al. Effects of levocetirizine and diphenhydramine on regional glucose metabolic changes and hemodynamic responses in the human prefrontal cortex during cognitive tasks. Hum Psychopharmacol. 2018;33(2):e2655.

Does Levocetirizine Dihydrochloride require protection from light during storage?

Yes, it is moderately photosensitive. Light exposure can cause discoloration and degradation. Store in light-resistant containers, preferably original opaque packaging.

What is the recommended storage temperature for Levocetirizine Dihydrochloride?

Store at controlled room temperature (15-25°C). Avoid excessive heat above 30°C, which can accelerate oxidation and loss of the dihydrochloride salt.

Is Levocetirizine Dihydrochloride stable in oral solution formulations?

Yes, when formulated with preservatives and protected from light.

How is the impurity levocetirizine R-enantiomer (the inactive isomer) monitored?

We use a validated chiral HPLC method to ensure enantiomeric purity (>99%) and monitor for the R-isomer during stability studies.