title: Antihistaminic and antiallergic properties of dextro-mequitamium iodide in upper and lower guinea pig airways: comparison with azelastine.
abstract: 1. The ability of dextro-mequitamium iodide (d-Meq) to antagonize bronchomotor and inflammatory effects mediated by histamine and antigen challenge in the upper or lower guinea pig airways or both and its potential 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 bronchodilating properties in the nanomolar range toward tonic contractions induced by histamine and carbachol. 3. d-Meq (100-1,000 nmol/guinea pig) and azelastine (100-5,000 nmol/guinea pig) administered by aerosol significantly inhibited histamine- and antigen-induced increases in insufflation pressure in sensitized animals. 4. d-Meq (1,000-6,000 nmol/kg i.v.) dose dependently inhibited the histamine- or antigen-induced increase in vascular permeability in the upper airways. 5. d-Meq was more effective against histamine than antigen challenge, and its potency was similar or greater than that of azelastine. 6. Aerosolized d-Meq (1,000 nmol/animal) reduced antigen-induced eosinophil accumulation in the bronchoalveolar lavage (BAL) fluid from sensitized guinea pigs. 7. Eosinophils recovered from the BAL fluid of antigen-challenged animals showed an increased chemotaxis in response to LTB4 or platelet-activating factor. Both d-Meq and azelastine (300 nmol/animal) reduced this increase without affecting direct chemotaxis induced by leukotriene B4 (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.
authors.affiliation: Pharmacology Department, Istituto Farmacobiologico Malesci, Florence, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Evangelista
authors.forename: P
authors.initials: P
authors.lastname: Boni
authors.forename: A
authors.initials: A
authors.lastname: Castellucci
authors.forename: F
authors.initials: F
authors.lastname: Perretti
authors.forename: M
authors.initials: M
authors.lastname: Pretolani
authors.forename: D
authors.initials: D
authors.lastname: Joseph
authors.forename: A R
authors.initials: AR
authors.lastname: Renzetti
authors.forename: A
authors.initials: A
authors.lastname: Subissi
authors.forename: S
authors.initials: S
authors.lastname: Manzini
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D002199:Capillary Permeability / Q000187:drug effects; D002417:Cattle; D002633:Chemotaxis / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007327:Insufflation; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D010640:Phenothiazines / Q000494:pharmacology*; D010793:Phthalazines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D018926:Anti-Allergic Agents; D006634:Histamine H1 Antagonists; D010640:Phenothiazines; D010793:Phthalazines; D010972:Platelet Activating Factor; C049967:LG 30435; D007975:Leukotriene B4; C020976:azelastine