Comparative Oral and Topical Decongestant Effects of Phenylpropanolamine and d-Pseudoephedrine

Nonselective adrenergic α-agonists such as phenylpropanolamine and d-pseudoephedrine are widely used as decongestants to treat nasal congestion associated with a variety of nasal diseases. Although the activity of these drugs is well established in clinical studies, a direct comparison of their nasal decongestant effect as determined by changes in nasal cavity dimensions and nasal architecture has not been studied. Using acoustic rhinometry, we evaluated the effects of these drugs on nasal cavity volume, minimum cross-sectional area (A_min), and the distance from the nosepiece to the A_min (D_min) in a feline, pharmacological model of nasal congestion. Administration of topical compound 48/80 (1%), a mast cell histamine liberator, into the left nasal passageway decreased nasal volume by 66%, reduced A_min by 51%, and increased D_min by 116%. The congestive responses to compound 48/80 (1%) were reproducible through six weeks. In a subset of cats, the nasal cavity volume effect of repetitive exposure to compound 48/80, given once every two weeks for six weeks, was not different from the nasal responses after the initial exposure to compound 48/80. Pretreatment with oral phenylpropanolamine (10 mg/kg) or oral d-pseudoephedrine (10 mg/kg) attenuated the nasal effects of compound 48/80, but were associated with a pronounced increase in systolic blood pressure of +51 and +82 mmHg, respectively. A similar decongestant profile was observed with phenylpropanolamine (1%) and d-pseudoephedrine (1%) when given topically. Topical phenylpropanolamine (1%) and d-pseudoephedrine (1%) 45 minutes after dosing increased blood pressure +44 and +17 mmHg, respectively, over control animals. We conclude that oral and topical phenylpropanolamine and d-pseudoephedrine display equieffective nasal decongestant activity and produce similar cardiovascular profiles characterized by significant increases in blood pressure.