Azelastine and desmethylazelastine suppress acetylcholine-induced contraction and depolarization in human airway smooth muscle

Richards, Ira S.; Miller, Larry S.; Solomon, David A.; Kulkarni, Arun P.; Brooks, Stuart M.; Sperelakis, Nick

doi:10.1016/0014-2999(90)90455-f

Cited by 7 publications

(2 citation statements)

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“…In conclusion, the preferential uptake of azelastine by the lung (2, 28, 31, this study), the tendency to accumulate in alveolar macrophages (31), its long half-life (2) and the relatively large amount of its major metabolite desmethylazelastine in the lungs (this study) could explain its ability to inhibit immediate and late allergic reactions (8, 16,21,22,24) and to interfere with the synthesis and release of mediators from inflammatory cells (3,5,10,11,12,15,(17)(18)(19)23,30), hyperpolarizing activity (26) in human airway smooth muscle or antagonism of KCl, BaClj, Ca^ ^, TEA, and other mediators in smooth muscles (6, unpublished observations). RD, Inhibition of allergic and nonallergic leukotriene C4 formation and histamine secretion by azelasline; implication for its mechanism of action, Int Arch Allergy Appl Immunol 1989; 90; 67-70,…”

Section: Discussionmentioning

confidence: 86%

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Pharmacodynamic and pharmacokinetic studies with azelastine in the guinea pig: evidence for preferential distribution into the lung

Chand

Adusumalli

Nolan

et al. 1993

Allergy

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The correlation between the antiasthma activity of azelastine and the concentrations of azelastine and its major metabolite, desmethylazelastine, in the blood and lung were investigated in guinea pigs. Blood and lung tissue samples collected at 15 min after aeroallergen (ovalbumin, 0.5 mg/ml, 30 s, 15 psi) challenge, i.e., 2-1/4 h after oral administration of the drug, were analyzed for azelastine and its desmethyl metabolite by specific HPLC assay. Azelastine afforded protection against immediate allergic responses (IAR, characterized by gasping and bronchospasmic convulsions). Based on the reduction of the severity of IAR, the ID50 was 0.04 mg/kg. It also delayed the onset of IAR and prevented mortalities. A positive correlation (r2 = 0.944) between the antiallergic activity and the sum concentrations of azelastine and desmethylazelastine in the lung was observed. Preferential uptake of azelastine and desmethylazelastine by the lung was demonstrated by the mean lung/blood ratio of about 22 and 146, respectively. The selective uptake of azelastine and its active metabolite by the lungs could contribute to its antiasthmatic/antiallergic activity in guinea pigs.

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Section: Discussionmentioning

confidence: 86%

“…The oral doses of azelastine HCl (0.1-3 mg/kg) yield a total lung concentration of 1.4 to 22.2 \iM for both azelastine and desmethylazelastine. This concentration range may be adequate to contribute to the antiallergy and pulmonary antiinflammatory activities reported in the experimental animals (5, 6, 10-13, 18,19,23,26,29,30).…”

Section: Discussionmentioning

confidence: 99%