The problem of cough and development of novel antitussives
The problem of cough and development of novel antitussives
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DOI：
10.1016/j.pupt.2006.11.001
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发表时间：
2007-01-01
影响因子：
3.2
通讯作者：
Barnes, Peter J.
中科院分区：
文献类型：
--
作者：
Barnes, Peter J.
咳嗽是一种非常常见的临床症状，目前的治疗方法基本上无效，这表明医疗需求尚未得到满足。迫切需要开发新颖且安全的镇咳疗法。这可能是由于更好地了解参与咳嗽的感觉神经和被激活的信号通路而产生的。主要的治疗目标应该是咳嗽反射的敏化，这是急性（病毒引起的）咳嗽和慢性咳嗽（包括慢性特发性咳嗽）患者的一个特征。对人类咳嗽机制的研究有限。目前正在探索几种新颖的治疗方法。也许最有前途的药物是瞬时受体电位香草酸-1 (TRPVI) 拮抗剂、选择性大麻素激动剂（CB2 激动剂）、maxi-K 通道开放剂和 P2X3 拮抗剂。新的咳嗽疗法可能针对气道神经敏化，并且最好以吸入器的形式提供，以尽量减少任何全身影响。了解伤害感受所涉及的细胞间信号传导途径可能会导致未来用于治疗咳嗽的新药物，例如 p38 丝裂原激活蛋白 (MAP) 激酶抑制剂。几种作为止痛药开发的新疗法也可能被证明对治疗咳嗽有益。 (c) 2006 Elsevier Ltd. 保留所有权利。
Cough is a very common clinical symptom and current therapies are largely ineffective, indicating a major unmet medial need. There is a pressing need to develop novel and safe antitussive therapies. This is likely to arise from better understanding of the sensory nerves involved in cough and the signalling pathways that are activated. A major therapeutic target should be sensitization of the cough reflex which is a feature of patients with both acute (virally induced) cough and chronic cough, including chronic idiopathic cough. Studies on human cough mechanisms are limited. There are several novel therapeutic approaches that are currently being explored. Perhaps the most promising drugs are transient receptor potential vanilloid-1 (TRPVI) antagonists, selective cannabinoid agonists (CB2 agonists), maxi-K channel openers and P2X3 antagonists. New cough therapies may target airway nerve sensitization and may best be delivered as inhalers to minimize any systemic effects. Understanding the intercellular signalling pathways involved in nociception may lead to novel drugs, such as p38 mitogen-activated protein (MAP) kinase inhibitors, being used in the treatment of cough in the future. It is also likely that several novel treatments that are developed as analgesics will also prove to be beneficial in the treatment of cough. (c) 2006 Elsevier Ltd. All rights reserved.