Azelastine | CAS 58581-89-8 | H₁ Antagonist | API
Product Name: Azelastine
CAS No.: 58581-89-8
Form: Crystalline hydrochloride salt
LogP: 4.2
pKa (basic N): ≈8.9
H₁ receptor affinity (Ki): ≈1.1 nM
Description
Azelastine is a selective H₁ antagonist with additional anti-leukotriene and anti-cholinergic activity. Topical formulations rapidly reduce rhinorrhea and conjunctival itching with minimal systemic effects. The safety profile is high.
1. Introduction
Second-generation antihistamines tend to have systemic effects. Azelastine, designed for topical administration, demonstrates distinct pharmacokinetics and a combination of mechanisms, addressing the niche of persistent allergic symptoms.
2. Structural Features
-
Form: Crystalline hydrochloride salt
-
Spatial configuration: The azepine ring provides high affinity for the H₁ receptor (Ki ≈ 1.1 nM)
-
LogP: 4.2
-
pKa (basic N): ≈8.9
3. Pharmacodynamics
| Mechanism | Effect |
|---|---|
| H₁ blockade | Inhibits G-protein-dependent IP₃ release, preventing intracellular Ca²⁺ flux |
| Mast cell stabilization | Reduces IL-4 and IL-6 release |
| PAF antagonism | Reduces late-phase allergic response |
| Eotaxin suppression | Inhibits eotaxin-induced eosinophil migration |
4. Pharmacokinetics
| Parameter | Value |
|---|---|
| Bioavailability (intranasal) | ≈40% |
| tₘₐₓ | 2 hours |
| V_d | ≈14 L/kg (pronounced tissue depot effect) |
| Metabolism | O-demethylation (CYP3A4) → desmethylazelastine (active; ~10% activity) |
| T½ | 22 hours |
| Clearance | 0.5 L/h/kg |
| Excretion | 75% fecal |
5. Clinical Data
Randomized studies (n > 2,500) showed a 50–70% reduction in nasal symptom index within 15 minutes.
-
Allergic conjunctivitis: Itching relief within 3–5 minutes, effect lasting 8–10 hours
-
Comparison with olopatadine: Azelastine provides longer-lasting control of sneezing (p < 0.05)
6. Safety Profile
| Side Effect | Incidence |
|---|---|
| Somnolence | <1% |
| Bitter taste | 12% |
| Epistaxis | <0.5% |
-
QT prolongation clinically insignificant
-
Long-term use (≤12 months) does not affect nasal mucosa per biopsy data
7. Regulatory Status
-
FDA and EMA approved for patients:
-
Nasal: ≥6 years (no duration restrictions)
-
Ophthalmic: ≥4 years (no duration restrictions)
-
-
WADA: Not prohibited
8. Future Perspectives
-
Chitosan-based mucoadhesive sprays – increased contact time, reduced dosage
-
Nanocrystalline ophthalmic gels with up to 24-hour prolongation
-
Combination with corticosteroids (fluticasone + azelastine) – proven synergy
9. Conclusion
High receptor selectivity, multi-target mechanism, and good tolerability make azelastine the gold standard for rapid relief of allergic symptoms. Its formulation flexibility opens opportunities for innovative drug delivery systems.
For pharmaceutical manufacturing use only. Not for direct human consumption.
