ANTIHISTAMINIC AND ANTIALLERGIC PROPERTIES OF DEXTRO-MEQUITAMIUM IODIDE IN UPPER AND LOWER GUINEA-PIG AIRWAYS - COMPARISON WITH AZELASTINE

1. The ability of dextro-mequitamium iodide (d-Meq) to antagonize bron chomotor and inflammatory effects mediated by histamine and antigen ch allenge in the upper or lower guinea pig airways or both and its poten tial activity against the recruitment and activation of eosinophils in the bronchial wall have been evaluated in comparison with azelastine. 2. In receptor-binding studies, d-Meq displayed a nanomolar affinity for H1 and muscarinic receptors, and it was endowed with potent bronch odilating properties in the nanomolar range toward tonic contractions induced by histamine and carbachol. 3. d-Meq (100-1,000 nmol/guinea pi g) and azelastine (100-5,000 nmol/guinea pig) administered by aerosol significantly inhibited histamine-and antigen-induced increases in ins ufflation pressure in sensitized animals. 4. d-Meq (1,000-6,000 nmol/k g IV) dose dependently inhibited the histamine or antigen-induced incr ease in vascular permeability in the upper airways. 5. d-Meq was more effective against histamine than antigen challenge, and its potency wa s similar or greater than that of azelastine. 6. Aerosolized d-Meq (1, 000 nmol/animal) reduced antigen-induced eosinophil accumulation in th e bronchoalveolar lavage (BAL) fluid from sensitized guinea pigs. 7. E osinophils recovered from the BAL fluid of antigen-challenged animals showed an increased chemotaxis in response to LTB4 or platelet-activat ing factor. Both d-Meq and azelastine (300 nmol/animal) reduced this i ncrease without affecting direct chemotaxis induced by leukotriene B-4 (LTB4). 8. These findings provide evidence that local administration of d-Meq might be useful in the treatment of allergic disorders, such as rhinitis and asthma. (C) 1998 Elsevier Science Inc.