氨溴索治疗神经病理性疼痛:藏在众目睽睽之下?
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浙江大学医学院附属第一医院疼痛科

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Ambroxol for neuropathic pain: hiding in plain sight?
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Department of Pain Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine

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    摘要:

    氨溴索是一种多功效药物,主要具有促黏液活性及溶解分泌物作用,同时具有抗炎、抗氧化和局部麻醉作用。其在治疗呼吸道疾病方面的使用历史悠久,缓解喉痛效果良好。近年来,氨溴索因其在治疗神经病理性疼痛方面的潜在用途而备受关注。明确的临床前证据提示氨溴索主要通过阻断感觉神经元上的电压门控钠离子(Nav)通道发挥镇痛作用,然而相关研究进展缓慢。氨溴索是Nav1.8和Nav1.7抑制剂,Nav1.8在神经病理性疼痛的病理生理机制中发挥重要作用,而Nav1.7则是治疗慢性疼痛的特异性兴奋靶点。本综述讨论了氨溴索的镇痛机制和协同作用机制,并回顾氨溴索治疗顽固性疼痛和神经病理性疼痛的临床前和临床研究,包括三叉神经痛、纤维肌痛综合征和复杂性区域疼痛综合征。氨溴索具有良好的安全性、广泛的临床前和临床药物研究数据、临床有效性的早期证据,因此氨溴索的重新利用值得进一步研究。氨溴索作为专利到期药物,应大力推动其治疗神经病理性疼痛的临床试验。本文鼓励制药行业开展专利药物配方研究,并大力推广优化版本。

    Abstract:

    Ambroxol is a multifaceted drug with primarily mucoactive and secretolytic actions, along with anti-inflammatory, antioxidant, and local anaesthetic properties. It has a long history of use in the treatment of respiratory tract diseases and has shown to be efficacious in relieving sore throat. In more recent years, ambroxol has gained interest for its potential usefulness in treating neuropathic pain. Research into this area has been slow, despite clear preclinical evidence to support its primary analgesic mechanism of action—blockade of voltage-gated sodium (Nav) channels in sensory neurons. Ambroxol is a commercially available inhibitor of Nav1.8, a crucial player in the pathophysiology of neuropathic pain, and Nav1.7, a particularly exciting target for the treatment of chronic pain. In this review, we discuss the analgesic mechanisms of action of ambroxol, as well as proposed synergistic properties, followed by the preclinical and clinical results of its use in the treatment of persistent pain and neuropathic pain symptoms, including trigeminal neuralgia, fibromyalgia, and complex regional pain syndrome. With its well-established safety profile, extensive preclinical and clinical drug data, and early evidence of clinical effectiveness, ambroxol is an old drug worthy of further investigation for repurposing. As a patent-expired drug, a push is needed to progress the drug to clinical trials for neuropathic pain. We encourage the pharmaceutical industry to look at patented drug formulations and take an active role in bringing an optimized version for neuropathic pain to market.

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  • 收稿日期:2023-06-13
  • 最后修改日期:2023-07-07
  • 录用日期:2023-09-07
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