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Am J Respir Crit Care Med：XEN-D0501并不能减小难治性咳嗽患者的咳嗽频率

2018-07-17 MedSci MedSci原创

XEN-D0501难治性咳嗽咳嗽频率
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吸入辣椒素（一种瞬时受体电位香草酸1（TRPV1）激动剂）加重咳嗽反应是慢性咳嗽患者的特征。虽然TRPV1拮抗剂（SB-705498）可减少辣椒素诱发的咳嗽，但是并不能减小慢性咳嗽患者的自发性咳嗽频率。 近日，一项临床前研究将XEN-D0501（一种有效的TRPV1拮抗剂）与SB-705498进行比较，以确定XEN-D0501是否值得进一步的临床试验。 在感觉神经活化中测定XEN-D0

吸入辣椒素（一种瞬时受体电位香草酸1（TRPV1）激动剂）加重咳嗽反应是慢性咳嗽患者的特征。虽然TRPV1拮抗剂（SB-705498）可减少辣椒素诱发的咳嗽，但是并不能减小慢性咳嗽患者的自发性咳嗽频率。

近日，一项临床前研究将XEN-D0501（一种有效的TRPV1拮抗剂）与SB-705498进行比较，以确定XEN-D0501是否值得进一步的临床试验。

在感觉神经活化中测定XEN-D0501和SB-705498对抗辣椒素的效果，并且在豚鼠中评估对抗辣椒素诱导的咳嗽的效果。20例顽固性慢性咳嗽患者参加了一项双盲，随机，安慰剂对照交叉研究，接受14天XEN-D0501（口服，4 mg，每日两次）或安慰剂治疗，评估清醒咳嗽频率（主要结果），辣椒素诱导咳嗽和患者自我报告的结果。

结果显示，XEN-D0501在抑制辣椒素诱导的豚鼠和人分离的迷走神经的去极化方面比SB-705498更有效，且效力高1000倍。在体内，XEN-D0501完全抑制了辣椒素诱导的咳嗽，而SB-705498需要100多倍的剂量才能达到相同的效果。在患者中，XEN-D0501明显降低了对辣椒素的最大咳嗽反应（相对于基线的平均改变：XEN-D0501, -19.3 ± 16.4咳嗽；安慰剂, -1.8 ± 5.8 coughs; P < 0.0001），但在自发清醒咳嗽频率上并无此效果（相对于基线的平均改变：XEN-D0501, -19.3 ± 16.4；安慰剂, -1.8 ± 5.8 咳嗽; P < 0.0001）。

综上所述，该研究结果表明，XEN-D0501在临床前和临床辣椒素诱导研究中表现出卓越的效力，但是仍然无法减小自发性咳嗽频率，因此TRPV1并不是难治性咳嗽的有效治疗靶点。

原始出处：

Belvisi MG, Birrell MA, et al., XEN-D0501, a Novel Transient Receptor Potential Vanilloid 1 Antagonist, Does Not Reduce Cough in Patients with Refractory Cough. Am J Respir Crit Care Med. 2017 Nov 15;196(10):1255-1263. doi: 10.1164/rccm.201704-0769OC.

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  1. [GetPortalCommentsPageByObjectIdResponse(id=1528491, encodeId=850615284914d, content=<a href='/topic/show?id=74b798601a1' target=_blank style='color:#2F92EE;'>#难治性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98601, encryptionId=74b798601a1, topicName=难治性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a1ef11916292, createdName=freve, createdTime=Thu Jul 19 13:19:00 CST 2018, time=2018-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1608979, encodeId=b7bc16089e915, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Thu Jul 19 13:19:00 CST 2018, time=2018-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332333, encodeId=35ba332333d8, content=学习了很有用, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Wed Jul 18 00:04:02 CST 2018, time=2018-07-18, status=1, ipAttribution=)]
    2018-07-19 freve

    #难治性#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1528491, encodeId=850615284914d, content=<a href='/topic/show?id=74b798601a1' target=_blank style='color:#2F92EE;'>#难治性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98601, encryptionId=74b798601a1, topicName=难治性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a1ef11916292, createdName=freve, createdTime=Thu Jul 19 13:19:00 CST 2018, time=2018-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1608979, encodeId=b7bc16089e915, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Thu Jul 19 13:19:00 CST 2018, time=2018-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332333, encodeId=35ba332333d8, content=学习了很有用, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Wed Jul 18 00:04:02 CST 2018, time=2018-07-18, status=1, ipAttribution=)]
    2018-07-19 ms3994565386320060

    #Med#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1528491, encodeId=850615284914d, content=<a href='/topic/show?id=74b798601a1' target=_blank style='color:#2F92EE;'>#难治性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98601, encryptionId=74b798601a1, topicName=难治性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a1ef11916292, createdName=freve, createdTime=Thu Jul 19 13:19:00 CST 2018, time=2018-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1608979, encodeId=b7bc16089e915, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Thu Jul 19 13:19:00 CST 2018, time=2018-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=332333, encodeId=35ba332333d8, content=学习了很有用, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Wed Jul 18 00:04:02 CST 2018, time=2018-07-18, status=1, ipAttribution=)]
    2018-07-18 飛歌

    学习了很有用

    0