Department of Neurobiology/Respiratory, Schering-Plough Research Institute, Kenilworth, N.J. 07033-0539, USA.
Pharmacology. 2010;85(5):259-63. doi: 10.1159/000284581. Epub 2010 Apr 7.
Nasal congestion is the most troublesome symptom associated with a variety of upper airway diseases, including allergic rhinitis and the common cold. A better understanding of the mechanisms that regulate nasal cavity caliber may engender the development of novel treatment strategies. It is well accepted that alpha-adrenergic (both alpha(1) and alpha(2)) mechanisms play a fundamental role in the control and maintenance of basal nasal patency. JP-1302 is a selective alpha(2c)-subtype antagonist that has been recently described in the scientific literature. Thus, we sought to examine the potential effects of this new pharmacological tool on basal nasal patency.
Using acoustic rhinometry, we studied the activity of the selective alpha(2c)-antagonist JP-1302 on nasal cavity volumes in an anesthetized cat. Cumulative concentrations of JP-1302 were applied directly into the right nasal cavity. Changes in the nasal cavity geometry of the drug-treated naris relative to the untreated left nasal cavity were determined. In separate studies, the nonselective alpha(2)-antagonist yohimbine and the nonselective alpha(1)-antagonist prazosin were run as comparators. Systolic blood pressure was measured at the hind leg, using an ultrasonic Doppler flow detector.
JP-1302 (0.03, 0.1, 0.3 and 1.0%) administered by the intranasal route decreased nasal cavity volumes from baseline values by 17, 25, 40 and 40%, respectively. Yohimbine (0.03, 0.1, 0.3 and 1.0%) decreased volumes by 19, 36, 46 and 53%, and topical administration of the nonselective alpha(1)-antagonist prazosin (0.001, 0.003, 0.01, 0.03 and 0.1%) decreased volumes by 6, 47, 56, 64 and 71%, respectively. JP-1302, yohimbine and prazosin, at the dose level tested, did not alter the blood pressure.
The present set of experiments indicates that both alpha(1)- and alpha(2)-adrenergic receptors are involved in the maintenance of basal nasal patency in the cat. Moreover, alpha(2c)-receptors may play a significant role in the sympathetic control of upper airway function.
鼻塞是与各种上呼吸道疾病相关的最恼人的症状，包括过敏性鼻炎和普通感冒。更好地理解调节鼻腔口径的机制可能会产生新的治疗策略。众所周知，α-肾上腺素能（α1 和 α2）机制在控制和维持基础鼻腔通畅中起着基本作用。JP-1302 是一种最近在科学文献中描述的选择性 α2c-亚型拮抗剂。因此，我们试图研究这种新的药理学工具对基础鼻腔通畅的潜在影响。
我们使用声鼻反射测量法研究了选择性 α2c-拮抗剂 JP-1302 在麻醉猫中对鼻腔容积的作用。将 JP-1302 的累积浓度直接应用于右侧鼻腔。与未处理的左侧鼻腔相比，药物处理的鼻腔的鼻腔几何形状变化被确定。在单独的研究中，作为比较剂，使用非选择性 α2-拮抗剂育亨宾和非选择性 α1-拮抗剂哌唑嗪。使用超声多普勒血流探测器在后腿测量收缩压。
经鼻途径给予 JP-1302（0.03、0.1、0.3 和 1.0%）可使鼻腔容积分别从基线值降低 17%、25%、40%和 40%。育亨宾（0.03、0.1、0.3 和 1.0%）使容积降低 19%、36%、46%和 53%，局部给予非选择性 α1-拮抗剂哌唑嗪（0.001、0.003、0.01、0.03 和 0.1%）使容积降低 6%、47%、56%、64%和 71%。在测试的剂量水平下，JP-1302、育亨宾和哌唑嗪均未改变血压。
本实验组表明，α1-和 α2-肾上腺素能受体均参与猫基础鼻腔通畅的维持。此外，α2c-受体可能在上呼吸道功能的交感神经控制中发挥重要作用。
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