Suzetrigine was approved by the US American Food and Drug Administration in 2025 as the first oral, non-opioid, selective inhibitor of NaV1.8 sodium channel for the treatment of acute pain. Therefore, it represents a groundbreaking advancement in pain management. This review aims to provide an overview of the milestones in the medicinal-chemical development of NaV1.8 inhibitors, eventually leading to suzetrigine. The multi-step synthesis route of suzetrigine is presented. Taking structural features into account, insights are provided into what plays a role for the inhibition of the NaV1.8 channel. In addition, pharmacodynamic and pharmacokinetic aspects of the new drug, such as bioavailability, metabolism, and interaction with CYP450 enzymes, are discussed. A summary based on a large number of clinical trials demonstrating remarkable efficacy completes this comprehensive drug profile of suzetrigine, while also addressing limitations of the clinical trials and suggesting future perspectives.
