Levocetirizine

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Cat Number

API130018778

CAS Number

130018-77-8

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CAS Number

130018-77-8

EINECS

1312995-182-4

Storage

Sealed in dry,2-8℃

Synonyms

alerlisin;LevocetirizineHydrochloride

Molecular Formula

C21H25ClN2O3

Molecular Weight

388.89

Smiles

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

Appearance

White to off-white solid

Melting Point

205-208℃

Boiling Point

542.1±45.0 ℃

Relative Density

1.237±0.06

General Description

Active R-enantiomer of cetirizine, levocetirizine, is a highly effective and well-tolerated selective second-generation antihistamine with relatively few side effects. Levocetirizine is also a first-line medication for the treatment of allergic rhinitis and chronic urticaria. It shows higher selectivity for peripheral H1 receptors and less anticholinergic activity in comparison with first-generation antihistamines, with fewer side effects affecting the central nervous system, and less tendency to cause drowsiness.

Mechanism of Action

Histamine is the most important inflammatory mediator released from mast cells during allergic inflammation and its actions are mediated by four G protein-coupled receptor subtypes (H1, H2, H3, and H4). Levocetirizine is a very potent and selective H1 receptor antagonist that inhibits the binding of endogenous histamine to the H1 receptor and thus blocks the four classic signs (capillary dilation, stimulation of sensory nerve endings, contraction of smooth muscle, and increased glandular secretion) that are evoked by histamine. In addition, it modulates the subsequent inflammatory phase of the allergic reaction by inhibiting the migration and activation of inflammatory cells and by inhibiting the release and expression of inflammatory mediators.

Application

The approved indication of levocetirizine is for the relief of allergy symptoms in adults and children (usually 6 months and older), including:
Allergic Rhinitis: Seasonal (hay fever) and year-round (perennial) allergic rhinitis. Levocetirizine reduces symptoms like sneezing, runny nose, nasal congestion, itchy nose, itchy eyes, and tearing.
Chronic Idiopathic Urticaria: It relieves symptoms like skin itching and wheals (hives).

Binding studies indicate that levocetirizine is a high-affinity, stereoselective ligand of the human histamine H₁ receptor. Levocetirizine is found to bind competitively to the human histamine H₁ receptor with subnanomolar to low-nanomolar affinity, hundreds of times greater affinity than either the S-enantiomer or racemic mixture. The high affinity binding of levocetirizine to the H₁ receptor is stereoselective, further implicating molecular shape as key for receptor recognition. Levocetirizine also possesses unique binding kinetics, dissociating slowly from the H₁ receptor. The high affinity and slow dissociation rate contribute to a long-lasting occupancy of the receptor, with antagonism of histamine that may seem resistant to surmountability (seemingly non-competitive) in tissue assays. Competitive binding studies of levocetirizine indicate that key residues within the H₁ receptor, including Lys191 and Thr194, appear to control affinity and slow off rates, suggesting specific ligand–receptor interactions contribute to a stabilized drug–receptor complex.

Fig. 1 Affinity of compounds for wild-type and mutant H1 receptors. (Gillard M.; et al. 2002)

References

Gillard M, et al. Binding characteristics of cetirizine and levocetirizine to human H(1) histamine receptors: contribution of Lys(191) and Thr(194). Mol Pharmacol. 2002 Feb;61(2):391-9.

Levocetirizine (LCZ) is a second-generation antihistamine, a drug with high efficacy and low side effects for the treatment of allergic diseases, mainly allergic rhinitis and chronic idiopathic urticaria. On the other hand, its half-life is only 7-8 hours, requiring daily administration which can lead to low adherence in pediatric patients. An synthesized two prodrugs of LCZ, LCZ decanoate (LCZ-D) and LCZ laurate (LCZ-L), by esterification with alkanols and characterized by nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC). Next, both prodrugs were mixed with oleaginous carriers (castor oil and benzyl benzoate) to prepare injectable preparations. Evaluation of their in vivo physicochemical stability, enzymatic hydrolysis, and pharmacokinetics, showed that both formulations showed potential for prolonged LCZ delivery keeping therapeutic plasma levels for more than 30 days.

Fig. 2 Chemical structures of levocetirizine and its prodrug derivatives.(Ahn JH.; et al. 2025)