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Background: Histamine and leukotrienes act to exert numerous local and systemic effects that contribute to the pathophysiology of allergic rhinitis. The aim of these experiments was to evaluate the nasal decongestant effects of loratadine and montelukast alone and in combination in a feline model of nasal congestion. We also studied the decongestant actions of the alpha-agonist adrenergic agonist D-pseudoephedrine with and without desloratadine. Methods: Acoustic rhinometry was used to determine nasal cavity dimensions after intranasal compound 48/80. Cats were given D-pseudoephedrine (0.3 mg/kg) alone or in combination with desloratadine (5 mg/kg) 1 hour before nasal provocation with compound 48/80 (1%, 75 microliters) to either the left or right nasal passageway. Using a similar design, the nasal decongestant effects of montelukast (1 mg/kg) and loratadine (10 mg/kg) were studied alone and in combination. Results: The addition of desloratadine to D-pseudoephedrine did not improve decongestant efficacy compared with each drug given individually. In contrast, when montelukast (1 mg/kg) was given in combination with loratadine (10 mg/kg), the decongestant activity was greater than when these drugs were administered separately. Sixty minutes after compound 48/80 provocation the nasal cavity volume ratio (volume ratio of the compound 48/80 treated/untreated nasal passageway) for the control, montelukast alone, loratadine alone, and the montelukast plus loratadine-treated groups were 0.20 ± 0.03, 0.24 ± 0.01, 0.28 ± 0.03, and 0.50 ± 0.03. Conclusion: Concomitant montelukast plus loratadine produces a greater degree of nasal decongestion compared with montelukast or loratadine alone in an experimental model of nasal congestion. [ABSTRACT FROM AUTHOR]