Erickson C H, McLeod R L, Mingo G G, Egan R W, Pedersen O F, Hey J A
Allergy, Schering-Plough Research Institute, Kenilworth, New Jersey 07033-0539, USA.
Am J Rhinol. 2001 Mar-Apr;15(2):83-90. doi: 10.2500/105065801781543772.
Nonselective adrenergic alpha-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 (Amin), and the distance from the nosepiece to the Amin (Dmin) 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 Amin by 51%, and increased Dmin 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.
非选择性肾上腺素能α-激动剂，如去氧肾上腺素和d-伪麻黄碱，被广泛用作减充血剂，以治疗与多种鼻部疾病相关的鼻充血。尽管这些药物的活性在临床研究中已得到充分证实，但尚未对它们通过鼻腔尺寸和鼻结构变化所确定的鼻减充血效果进行直接比较。我们使用鼻声反射仪，在猫的鼻充血药理学模型中评估了这些药物对鼻腔容积、最小横截面积（Amin）以及从鼻前庭到Amin的距离（Dmin）的影响。向左侧鼻道局部施用肥大细胞组胺释放剂复方48/80（1%），可使鼻腔容积减少66%，Amin降低51%，Dmin增加116%。对复方48/80（1%）的充血反应在六周内可重复出现。在一部分猫中，每两周重复暴露于复方48/80一次，持续六周，其鼻腔容积效应与初次暴露于复方48/80后的鼻腔反应并无差异。口服去氧肾上腺素（10 mg/kg）或口服d-伪麻黄碱（10 mg/kg）预处理可减弱复方48/80的鼻效应，但分别伴有收缩压显著升高+51和+82 mmHg。局部施用去氧肾上腺素（1%）和d-伪麻黄碱（1%）时观察到类似的减充血情况。给药45分钟后，局部施用去氧肾上腺素（1%）和d-伪麻黄碱（1%）的猫的血压分别比对照动物升高+44和+17 mmHg。我们得出结论，口服和局部施用去氧肾上腺素以及d-伪麻黄碱具有等效的鼻减充血活性，并产生以血压显著升高为特征的类似心血管反应。
