Current research status of sigma-1 receptor as a therapeutic target for anxiety disorders

Anxiety disorder, as a psychiatric condition characterized by high prevalence, chronic progression, and frequent comorbidities, faces significant limitations with current clinical treatments such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and benzodiazepines. These therapies are often constrained by limited efficacy, notable side effects, and issues of drug resistance. In recent years, the sigma-1 receptor has emerged as a promising target for novel anti-anxiety medications, with its ligands demonstrating significant anxiolytic effects in various animal models, offering new hope for addressing current therapeutic challenges. However, no anti-anxiety drugs targeting the sigma-1 receptor have advanced to clinical research stages. Therefore, this article reviews recent progress in understanding the molecular mechanisms of the sigma-1 receptor in anxiety disorders and summarizes the pharmacological efficacy of its ligands in animal models, aiming to provide a theoretical foundation and research directions for the development of innovative anti-anxiety drugs targeting the sigma-1 receptor.