Peshin Supriya, Villa Celi Claudia, Rashid Saima, Rego Asti, Baumrucker Steven J
Department of Internal Medicine, Norton Community Hospital, Norton, VA, USA.
Department of Internal Medicine, Capital Health, New York, NY, USA.
Am J Hosp Palliat Care. 2025 Jul 2:10499091251353455. doi: 10.1177/10499091251353455.
Suzetrigine (formerly known as VX-548) is a novel sodium channel inhibitor that selectively targets NaV1.8, a key mediator in pain signal transmission, particularly in peripheral nociceptive neurons. This mechanism distinguishes suzetrigine from traditional opioid therapies, offering an effective alternative for acute pain management without the risks of addiction, sedation, or respiratory depression commonly associated with opioids. This literature review examines the pharmacology, mechanism of action, and clinical efficacy of suzetrigine, with an emphasis on its role in acute pain reduction, safety profile, and emerging clinical applications. Preclinical research on suzetrigine and earlier NaV1.8 inhibitors has demonstrated significant reductions in nociceptive behaviors in animal models of inflammatory and neuropathic pain, with minimal off-target effects on other sodium channels such as NaV1.7 and NaV1.9. Unlike opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), suzetrigine acts by selectively inhibiting NaV1.8 channels, which play a specialized role in pain amplification, while sparing central nervous system pathways. In Phase 2 clinical trials involving patients undergoing bunionectomy and abdominoplasty, suzetrigine achieved significant reductions in postoperative pain compared to placebo and demonstrated analgesic efficacy comparable to hydrocodone/acetaminophen. This review highlights the advantages of suzetrigine over current pain management drugs, particularly its ability to relieve pain without side the unwanted side effects from opioids. Suzetrigine has been well-tolerated in both preclinical and clinical settings, with mild gastrointestinal symptoms reported as the most common adverse effect. Its selective mechanism makes suzetrigine a strong candidate for use in multimodal analgesic regimens, especially in postoperative care or among patients at risk for opioid misuse. In the context of the ongoing opioid crisis, suzetrigine represents a promising advancement in acute pain treatment. However, further research is needed to evaluate its long-term safety and efficacy, especially in chronic pain conditions and in combination with other analgesics. As its clinical use expands, suzetrigine may offer a critical tool for reducing opioid dependency across both acute and long-term pain management strategies.
舒泽曲明（曾用名VX - 548）是一种新型钠通道抑制剂，它选择性作用于NaV1.8，NaV1.8是疼痛信号传递中的关键介质，尤其是在外周伤害性神经元中。这一作用机制使舒泽曲明有别于传统的阿片类疗法，为急性疼痛管理提供了一种有效的替代方案，且不存在与阿片类药物相关的成瘾、镇静或呼吸抑制风险。这篇文献综述探讨了舒泽曲明的药理学、作用机制和临床疗效，重点关注其在减轻急性疼痛方面的作用、安全性概况以及新兴的临床应用。对舒泽曲明和早期NaV1.8抑制剂的临床前研究表明，在炎症性和神经性疼痛的动物模型中，伤害性反应行为显著减少，对其他钠通道如NaV1.7和NaV1.9的脱靶效应极小。与阿片类药物和非甾体抗炎药（NSAIDs）不同，舒泽曲明通过选择性抑制NaV1.8通道发挥作用，NaV1.8通道在疼痛放大中起特殊作用，同时不影响中枢神经系统通路。在涉及拇囊炎切除术和腹部整形术患者的2期临床试验中，与安慰剂相比，舒泽曲明显著减轻了术后疼痛，并且显示出与氢可酮/对乙酰氨基酚相当的镇痛效果。这篇综述强调了舒泽曲明相对于当前疼痛管理药物的优势，特别是其在不产生阿片类药物不良副作用的情况下缓解疼痛的能力。舒泽曲明在临床前和临床环境中耐受性良好，报告的最常见不良反应为轻度胃肠道症状。其选择性作用机制使舒泽曲明成为多模式镇痛方案中的有力候选药物，尤其是在术后护理或有阿片类药物滥用风险的患者中。在持续的阿片类药物危机背景下，舒泽曲明代表了急性疼痛治疗方面的一项有前景的进展。然而，需要进一步研究来评估其长期安全性和疗效，特别是在慢性疼痛病症以及与其他镇痛药联合使用时。随着其临床应用的扩大，舒泽曲明可能为在急性和长期疼痛管理策略中减少阿片类药物依赖提供一个关键工具。
