INTRODUCTION Clozapine-induced sialorrhea (CIS) is one of the most common side effects of clozapine use, while the mechanism remains unclear. METHODS A total of 51 schizophrenia patients taking clozapine were selected. Among them, 32 had sialorrhea, and 19 had no sialorrhea. Saliva metabolites were identified using ultra-high-performance liquid chromatography-MS/MS (UHPLC-MS/MS), and the differences in saliva metabolites in each group were analyzed through qualitatively searching HMDB, KEGG, and self-built databases, combined with multivariate statistics. After further evaluation by receiver-operating characteristic curve (ROC) analysis, the screened differential metabolites were enriched and topologically analyzed. RESULTS The biomarkers potentially related to CIS included 37 differential metabolites involving 17 metabolic pathways, mainly histidine metabolism (p < 0.05, impact = 0.50), pyrimidine metabolism (p < 0.05, impact = 0.08), and β-alanine metabolism (p < 0.05, impact = 0.06). CONCLUSION Our study indicates that histidine metabolic pathway may contribute to the mechanism of CIS.

中文翻译：

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基于非靶向代谢组学，组氨酸代谢途径导致氯氮平诱导的流涎。

简介 氯氮平引起的流涎（CIS）是氯氮平使用最常见的副作用之一，但其机制尚不清楚。方法选取服用氯氮平的精神分裂症患者51例。其中，有流涎者32人，无流涎者19人。采用超高效液相色谱-MS/MS（UHPLC-MS/MS）对唾液代谢物进行鉴定，通过定性检索HMDB、KEGG、自建数据库，结合多元统计。通过受试者工作特征曲线（ROC）分析进一步评估后，对筛选出的差异代谢物进行富集和拓扑分析。结果 与 CIS 潜在相关的生物标志物包括 37 种差异代谢物，涉及 17 条代谢途径，主要是组氨酸代谢（p < 0.05，影响 = 0.50）、嘧啶代谢（p < 0.05，影响 = 0.08）和 β-丙氨酸代谢（p < 0.05） ，影响= 0.06）。结论我们的研究表明组氨酸代谢途径可能有助于CIS的机制。